Adhesion Domains Research Articles

The Relationship between Mutations in Gene-Specific Domains of Salivary Fibronectin (cFn) and Dynamin-2 (Dynm-2) and the Development of Porphyromonas gingivalis-Initiated Periodontitis

Periodontitis is a chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. Its high prevalence and negative effects on quality of life make it one of the current problems in dentistry. Porphyromonas gingivalis (P. gingivalis) is the predominant periodontal pathogen that expresses a number of virulence factors involved in the pathogenesis of periodontitis. P. gingivalis fimbriae are a critical factor in the interaction between the organism and the host tissue. They promote both bacterial adhesion and invasion into the target sites. Fimbriae are capable of binding to human saliva components, extracellular matrix proteins, and commensal bacteria, as well as firmly binding to the cellular integrin α5β1. After attachment to α5β1-integrin, P. gingivalis is captured by cellular pseudopodia, which makes invagination through an actin-mediated pathway possible. It has been proven that the invagination event also requires the participation of the host cell dynamin, actin fibers, microtubules and lipid rafts. Work has emerged investigating mutations in the proline-rich terminal domain (PRD) and their impact on disease development. Salivary antimicrobial peptides are early protective factors against microbial attack. Of great interest is fibronectin (FN) as the main competitor of P. gingivalis fimbriae. The FN can interact with cells in three different regions: the central cell-binding domain (CCBD), the COOH terminal heparin-binding domain (Hep2), and the type III connecting segment (IIICS), including the CS1 region (Yamada, 1991). CCBD is the major cell-adhesion domain of FN and contains an Arg–Gly–Asp (RGD) motif that is recognized by members of the cell adhesion receptor integrin family, including a5b1, which is the primary FN receptor in many cell types. The work focuses on identifying the relationship between the development of periodontitis and the presence of mutations in the adhesion domains of salivary proteins such as cellular fibronectin (cFN) and dynamin-2 (DYNM2).

Complete genome sequences of Lacticaseibacillus paracasei INIA P272 (CECT 8315) and Lacticaseibacillus rhamnosus INIA P344 (CECT 8316) isolated from breast-fed infants reveal probiotic determinants

Lacticaseibacillus paracasei INIA P272 and Lacticaseibacillus rhamnosus INIA P344, isolated from breast-fed infants, are two promising bacterial strains for their use in functional foods according to their demonstrated probiotic and technological characteristics. To better understand their probiotic characteristics and evaluate their safety, here we report the draft genome sequences of both strains as well as the analysis of their genetical content. The draft genomes of L. paracasei INIA P272 and L. rhamnosus INIA P344 comprise 3.01 and 3.26 Mb, a total of 2994 and 3166 genes and a GC content of 46.27 % and 46.56 %, respectively. Genomic safety was assessed following the EFSA guidelines: the identification of both strains was confirmed through Average Nucleotide Identity, and the absence of virulence, pathogenic and antibiotic resistance genes was demonstrated. The genome stability analysis revealed the presence of plasmids and phage regions in both genomes, however, CRISPR sequences and other mechanisms to fight against phage infections were encoded. The probiotic abilities of both strains were supported by the presence of genes for the synthesis of SCFA, genes involved in resistance to acid and bile salts or a thiamine production cluster. Moreover, the encoded exopolysaccharide biosynthesis genes could provide additional protection against the deleterious gastrointestinal conditions, besides which, playing a key role in adherence and coaggregation of pathogenic bacteria together with the high number of adhesion proteins and domains encoded by both genomes. Additionally, the bacteriocin cluster genes found in both strains, could provide an advantageous ability to compete against pathogenic bacteria. This genomic study supports the probiotic characteristics described previously for these two strains and satisfies the safety requirements to be used in food products.

Development and Use of a Monoclonal Antibody Specific for the Candida albicans Cell-Surface Protein Hwp1.

The Candida albicans cell-surface protein Hwp1 functions in adhesion to the host and in biofilm formation. A peptide from the Gln-Pro-rich adhesive domain of Hwp1 was used to raise monoclonal antibody (MAb) 2-E8. MAb 2-E8 specificity for Hwp1 was demonstrated using a hwp1/hwp1 C. albicans isolate and strains that expressed at least one HWP1 allele. Immunofluorescence and atomic force microscopy experiments using MAb 2-E8 confirmed C. albicans germ-tube-specific detection of the Hwp1 protein. MAb 2-E8 also immunolabeled the tips of some Candida dubliniensis germ tubes grown under conditions that maximized HWP1 expression. The phylogeny of HWP1 and closely related genes suggested that the Gln-Pro-rich adhesive domain was unique to C. albicans and C. dubliniensis focusing the utility of MAb 2-E8 on these species. This new reagent can be used to address unanswered questions about Hwp1 and its interactions with other proteins in the context of C. albicans biology and pathogenesis.

Large-Scale Discovery of Microbial Fibrillar Adhesins and Identification of Novel Members of Adhesive Domain Families

ABSTRACTFibrillar adhesins are bacterial cell surface proteins that mediate interactions with the environment, including host cells during colonization or other bacteria during biofilm formation. These proteins are characterized by a stalk that projects the adhesive domain closer to the binding target. Fibrillar adhesins evolve quickly and thus can be difficult to computationally identify, yet they represent an important component for understanding bacterium-host interactions. To detect novel fibrillar adhesins, we developed a random forest prediction approach based on common characteristics we identified for this protein class. We applied this approach to Firmicutes and Actinobacteria proteomes, yielding over 6,500 confidently predicted fibrillar adhesins. To verify the approach, we investigated predicted fibrillar adhesins that lacked a known adhesive domain. Based on these proteins, we identified 24 sequence clusters representing potential novel members of adhesive domain families. We used AlphaFold to verify that 15 clusters showed structural similarity to known adhesive domains, such as the TED domain. Overall, our study has made a significant contribution to the number of known fibrillar adhesins and has enabled us to identify novel members of adhesive domain families involved in bacterial pathogenesis.IMPORTANCE Fibrillar adhesins are a class of bacterial cell surface proteins that enable bacteria to interact with their environment. We developed a machine learning approach to identify fibrillar adhesins and applied this classification approach to the Firmicutes and Actinobacteria Reference Proteomes database. This method allowed us to detect a high number of novel fibrillar adhesins and also novel members of adhesive domain families. To confirm our predictions of these potential adhesin protein domains, we predicted their structure using the AlphaFold tool.

Hydrogen‐Deuterium Exchange Identifies the Structural Basis of Phase Separation of the Chromosome Passenger Complex

The centromere is the locus that directs accurate chromosome segregation, and a master regulatory complex, the chromosome passenger complex (CPC) is enriched in a region of the mitotic centromere termed the inner centromere. In mitosis, the CPC monitors the connections of the centromere to the mitotic spindle, acting to destabilize incorrect attachments but permitting correct attachments to persist. The CPC contains the Aurora‐B kinase and three regulatory subunits: INCENP, Survivin and Borealin. Recent findings support a role for CPC phase separation in its localization and function in mitotic error correction (Trivedi et al., 2019, Nat. Cell Biol. 21:1127‐1137). Liquid‐liquid phase separation is emerging as a central regulatory principle of cell biology. This form of phase separation is often driven by multivalency of adhesive domains and/or linear motifs. The sequences of these domains are often found in unstructured regions where they are enriched in uncharged polar side chains, charged amino acids, or aromatic residues; additionally, structural plasticity allows them to generate multiple, weakly‐adhesive, inter‐ and intramolecular interactions. Currently there are no techniques to globally map the motifs on proteins that drive the multivalent interactions. In this context, we now employ hydrogen/deuterium exchange coupled to mass spectrometry (HXMS) to study dynamics of CPC phase separation. We have identified four regions within the regulatory CPC subunits that upon phase separation exhibit differential HX (three slower and one faster). Importantly, three of these regions map to structured regions of proteins while one maps to the expected intrinsically disordered regions. Each of the four regions is enriched with charged amino acids. Mutation of key residues in one of the differential HX regions within the INCENP subunit diminish droplet size and quantity, suggesting that we have successfully mapped a key surface for the phase separation properties of the CPC. In broader context we have shown for the first time how HXMS coupled with structural data and bioinformatic analysis can be applied to study molecular basics of protein liquid‐liquid phase separation.

Thrombospondin Related Anonymous Protein Superfamily in Vector-Borne Apicomplexans: The Parasite's Toolkit for Cell Invasion.

Apicomplexan parasites transmitted by vectors, including Babesia spp. and Plasmodium spp., cause severe disease in both humans and animals. These parasites have a complex life cycle during which they migrate, invade, and replicate in contrasting hosts such as the mammal and the invertebrate vector. The interaction of parasites with the host cell is mediated by adhesive proteins which play a key role in the different cellular processes regarding successful progression of the life cycle. Thrombospondin related anonymous protein (TRAP) is a superfamily of adhesins that are involved in motility, invasion and egress of the parasite. These proteins are stored and released from apical organelles and have either one or two types of adhesive domains, namely thrombospondin type 1 repeat and von Willebrand factor type A, that upon secretion are located in the extracellular portion of the molecule. Proteins from the TRAP superfamily have been intensively studied in Plasmodium species and to a lesser extent in Babesia spp., where they have proven to be functionally relevant throughout the entire parasite’s journey both in the arthropod vector and in the mammalian host. In recent years new findings provided answers to the role of TRAP proteins and in some cases the function of these adhesins during the parasite’s life cycle was redefined. In this review we will discuss the current knowledge of the diverse roles of the TRAP superfamily in vector-borne parasites from Class Aconoidasida. We will focus on the varied approaches that allowed the understanding of protein function and the relevance of TRAP- superfamily throughout the entire parasite’s cell cycle.

Elastic versus brittle mechanical responses predicted for dimeric cadherin complexes

Cadherins are a superfamily of adhesion proteins involved in a variety of biological processes that include the formation of intercellular contacts, the maintenance of tissue integrity, and the development of neuronal circuits. These transmembrane proteins are characterized by ectodomains composed of a variable number of extracellular cadherin (EC) repeats that are similar but not identical in sequence and fold. E-cadherin, along with desmoglein and desmocollin proteins, are three classical-type cadherins that have slightly curved ectodomains and engage in homophilic and heterophilic interactions through an exchange of conserved tryptophan residues in their N-terminal EC1 repeat. In contrast, clustered protocadherins are straighter than classical cadherins and interact through an antiparallel homophilic binding interface that involves overlapped EC1 to EC4 repeats. Here we present molecular dynamics simulations that model the adhesive domains of these cadherins using available crystal structures, with systems encompassing up to 2.8 million atoms. Simulations of complete classical cadherin ectodomain dimers predict a two-phased elastic response to force in which these complexes first softly unbend and then stiffen to unbind without unfolding. Simulated α, β, and γ clustered protocadherin homodimers lack a two-phased elastic response, are brittle and stiffer than classical cadherins and exhibit complex unbinding pathways that in some cases involve transient intermediates. We propose that these distinct mechanical responses are important for function, with classical cadherin ectodomains acting as molecular shock absorbers and with stiffer clustered protocadherin ectodomains facilitating overlap that favors binding specificity over mechanical resilience. Overall, our simulations provide insights into the molecular mechanics of single cadherin dimers relevant in the formation of cellular junctions essential for tissue function.

Tethering Piezo channels to the actin cytoskeleton for mechanogating via the cadherin-β-catenin mechanotransduction complex.

The mechanically activated Piezo channel plays a versatile role in conferring mechanosensitivity to various cell types. However, how it incorporates its intrinsic mechanosensitivity and cellular components to effectively sense long-range mechanical perturbation across a cell remains elusive. Here we show that Piezo channels are biochemically and functionally tethered to the actin cytoskeleton via the cadherin-β-catenin mechanotransduction complex, whose perturbation significantly impairs Piezo-mediated responses. Mechanistically, the adhesive extracellular domain of E-cadherin interacts with the cap domain of Piezo1, which controls the transmembrane gate, while its cytosolic tail might interact with the cytosolic domains of Piezo1, which are in close proximity to its intracellular gates, allowing a direct focus of adhesion-cytoskeleton-transmitted force for gating. Specific disruption of the intermolecular interactions prevents cytoskeleton-dependent gating of Piezo1. Thus, we propose a force-from-filament model to complement the previously suggested force-from-lipids model for mechanogating of Piezo channels, enabling them to serve as versatile and tunable mechanotransducers.

Calcium regulates the interplay between the tight junction and epithelial adherens junction at the plasma membrane.

The apical junctional complex (AJC) is a membrane protein ultrastructure that regulates cell adhesion and homeostasis. The tight junction (TJ) and the adherens junction (AJ) are substructures of the AJC. The interplay between TJ and AJ membrane proteins to assemble the AJC remains unclear. We employed synthetic biology strategies to express the basic membrane elements of a simple AJC-the adhesive extracellular domains of junctional adhesion molecule A (JAM-A), epithelial cadherin, claudin 1, and occludin-to study their interactions. Our results suggest that calcium concentration fluctuations and JAM-A, acting as an interface molecule between the TJ and AJ, orchestrate their interplay. Calcium affects the secondary structure, oligomerization, and binding affinity of homotypic and heterotypic interactions of TJ and AJ components, thus acting as a molecular switch influencing AJC dynamics.

Using Genomics to Shape the Definition of the Agglutinin-Like Sequence (ALS) Family in the Saccharomycetales.

The Candida albicans agglutinin-like sequence (ALS) family is studied because of its contribution to cell adhesion, fungal colonization, and polymicrobial biofilm formation. The goal of this work was to derive an accurate census and sequence for ALS genes in pathogenic yeasts and other closely related species, while probing the boundaries of the ALS family within the Order Saccharomycetales. Bioinformatic methods were combined with laboratory experimentation to characterize 47 novel ALS loci from 8 fungal species. AlphaFold predictions suggested the presence of a conserved N-terminal adhesive domain (NT-Als) structure in all Als proteins reported to date, as well as in S. cerevisiae alpha-agglutinin (Sag1). Lodderomyces elongisporus, Meyerozyma guilliermondii, and Scheffersomyces stipitis were notable because each species had genes with C. albicans ALS features, as well as at least one that encoded a Sag1-like protein. Detection of recombination events between the ALS family and gene families encoding other cell-surface proteins such as Iff/Hyr and Flo suggest widespread domain swapping with the potential to create cell-surface diversity among yeast species. Results from the analysis also revealed subtelomeric ALS genes, ALS pseudogenes, and the potential for yeast species to secrete their own soluble adhesion inhibitors. Information presented here supports the inclusion of SAG1 in the ALS family and yields many experimental hypotheses to pursue to further reveal the nature of the ALS family.

Beetle and mussel-inspired chimeric protein for fabricating anti-icing coating

Ice accretion on surfaces can cause serious damages and economic losses in industries and civilian facilities. Antifreeze proteins (AFPs) as evolutionary adaptation products of organisms to cold climates, provide solutions for alleviating icing problems. In this work, a chimeric protein Mfp-AFP was rationally designed combining mussel-inspired adhesive domain with Tenebrio molitor-derived antifreeze protein domain. Expectedly, the multifunctional Mfp-AFP can lower the freezing point of water and inhibit ice recrystallization. The chimeric protein could also readily modify diverse solid surfaces due to the adhesive domain containing Dopa, and resist frosting and delay ice formation due to the beetle-derived antifreeze fragment. Moreover, Mfp-AFP coatings display excellent biocompatibility proved by cytocompatibility and hemolysis assays. Here, the designed multifunctional protein coatings provide an alternative strategy for fabricating anti-icing surfaces.

Using recombinant adhesive proteins as durable and green flame-retardant coatings

Current fire retardants are known to be toxic to humans and our environment. As environmental-friendly flame retardants (FRs), protein-based flame retardants have been studied extensively recently, even though they are not durable. In this study, we designed, synthesized and tested a durable protein-based FR through the fusion of the adhesion domain from either mussel foot protein-5 (mfp-5) or cellulose-binding domain (CBD) with flame retardant protein (SR protein and alpha casein). We first verified the expression of the recombinant proteins in Escherichia coli using Western blot. Then, we coated the fusion protein (carrying cell lysates) to cotton fabrics and wood and verified with Infrared (IR) spectroscopy. Using a vertical burning test and wood flammability test, we confirmed the flame retardancy of the materials after the protein coating. In the vertical burning test, the SR protein and alpha casein flame retardant proteins with the CBD adhesion domain showed a 50.0% and 43.3% increase in flame retardancy. The data is also consistent in the wood flame retardancy test. Confocal imaging experiments also suggested these new fire retardants can be preserved on the materials well even after washing. Overall, our results showed that flame-retardant proteins with adhesion domains are high potential candidates of green alternative flame retardants.

In Vivo CRISPR-Cas9 Screens in PDX Models Reveals ADAM10 As Novel Therapeutic Target in Acute Leukemia

Acute leukemias require more accurate and effective treatments, especially upon disease relapse. In search for novel therapeutic targets for acute leukemias, we established a pipeline for CRISPR-Cas9 mediated functional genomic screens which harbor the ability to elegantly increase our knowledge about vulnerabilities and gene dependencies. For a highly patient-related setting, we performed CRISPR knockout (KO) dropout screens in patient-derived xenograft (PDX) models in vivo, combining the advantages of studying an individual patient´s tumor cell in the physiologic in vivo bone marrow microenvironment.Serially transplantable PDX models were lentivirally transduced to stably express Cas9. A customized CRISPR-Cas9 library targeting about 100 genes addressing surface molecules was designed, cloned and transduced into two PDX models of acute lymphoblastic leukemia (ALL). Enriched PDX ALL cells were transplanted into NSG mice and grown until advanced disease stage. Input versus end stage cells were subjected to next generation sequencing, followed by data analysis using MAGeCK algorithm. Data analysis revealed commonly depleted as well as sample-specific depleted genes between the two PDX models tested, and CXCR4 and ITGB1 were the top commonly depleted genes from the screens.For target validation, single sgRNA were cloned into the knockout vector; concomitant expression of recombinant fluorochromes allowed competitive growth assays in PDX models in vivo, comparing cells with KO of interest versus control KO in the same animal. In vivo competitive assay showed that both PDX models clearly depended on both CXCR4 and ITGB1, validating an essential function for both genes in the two PDX ALL models.Of note, disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was among the list of dropout genes in the screens. ADAM10 is known for its role in the central nervous system and considered as a therapeutic target in Alzheimer disease, but poorly studied in the context of leukemia. In competitive validation assays in vivo, ADAM10 KO population showed a clear growth disadvantage compared to control KO cells in a number of PDX models of ALL, but also acute myeloid leukemia (AML); in some PDX models, ADAM10 KO cells were completely abrogated, indicating that ADAM10 plays an essential role for different types of acute leukemias and represents a yet unknown vulnerability.To better characterize the role of ADAM10 for the clinical situation, we performed further in vivo assays with PDX models. Re-expression of ADAM10 in ADAM10 KO PDX cells could partially rescue the phenotype in an in vivo competitive reconstitution assay, unequivocally proving ADAM10 essentiality in ALL cells. Interestingly, a similar rescue assay expressing a ADAM10 variant lacking the disintegrin domain resulted in the same phenotypical compensation, highlighting essentiality of the enzymatic but not adhesion domain of ADAM10 in tumor engraftment and growth in BM. Important for translating the molecular insights into clinical use, PDX cells treated with an ADAM10 chemical inhibitor ex vivo, showed reduced tumor engraftment capacity compared to the vehicle treated cells, suggesting a role for ADAM10 in tumor-niche interactions and homing to the bone marrow. Further, we performed limiting dilution transplantation assays to determine stem cell frequencies; ADAM10 loss resulted in reduced stemness and a reduced number of leukemia-initiating cells compared to control KO cells, indicating that ADAM10 is essential also in leukemia stem cells. Of clinical relevance, ADAM10 KO significantly sensitized leukemic cells towards treatment of mice with the routine chemotherapeutic drug Cyclophosphamide in vivo, suggesting a putative synergistic effect when addressing ADAM10 as a therapeutic target.In summary, our data revealed ADAM10 as attractive novel vulnerability in acute leukemias with essential function for the tumor-niche interaction, leukemia stem cells and anti-leukemia treatment. ADAM10 might be addressed as therapeutic target to treat acute leukemias in the future. DisclosuresNo relevant conflicts of interest to declare.

Criticality in Cell Adhesion

We illuminate the many-body effects underlying the structure, formation, and dissolution of cellular adhesion domains in the presence and absence of forces. We consider mixed Glauber-Kawasaki dynamics of a two-dimensional model of nearest-neighbor interacting adhesion bonds with intrinsic binding-affinity under the action of a shared pulling or pushing force. We consider adhesion bonds that are immobile due to being anchored to the underlying cytoskeleton as well as adhesion molecules that are transiently diffusing. Highly accurate analytical results are obtained on the pair-correlation level of the Bethe-Guggenheim approximation for the complete thermodynamics and kinetics of adhesion clusters of any size, including the thermodynamic limit. A new kind of dynamical phase transition is uncovered -- the mean formation and dissolution times per adhesion bond change discontinuously with respect to the bond-coupling parameter. At the respective critical points cluster formation and dissolution are fastest, while the statistically dominant transition path undergoes a qualitative change -- the entropic barrier to complete binding/unbinding is rate-limiting below, and the phase transition between dense and dilute phases above the dynamical critical point. In the context of the Ising model the dynamical phase transition reflects a first-order discontinuity in the magnetization-reversal time. Our results provide a potential explanation for the mechanical regulation of cell adhesion, and suggest that the quasi-static and kinetic response to changes in the membrane stiffness or applied forces is largest near the statical and dynamical critical point, respectively.

Adhesion Class GPCRs in GtoPdb v.2021.3

Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [9] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [101, 403]. Several receptors have been suggested to function as mechanosensors [309, 280, 383, 35]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [122].

Extracellular AGR2 activates neighboring fibroblasts through endocytosis and direct binding to β-catenin that requires AGR2 dimerization and adhesion domains

Anterior gradient 2 (AGR2) is often overexpressed in several types of cancer. AGR2 is cytoplasmic or secreted as an extracellular signal. Intracellular AGR2 properties and role in cancer have been well studied, but its extracellular function is largely unclear. It has been shown that extracellular AGR2 activates endothelial cells and fibroblasts in culture, but the mechanism of AGR2 signaling is not well elucidated. Here, we report that tumor secreted or externally added AGR2 translocates into cytoplasm by endocytosis, binds to β-catenin and further co-translocates to the nucleus in NIH3T3 fibroblasts. Externally added AGR2 also increased β-catenin expression, stability, and accumulation in the nucleus in both fibroblasts and cancer cells. External AGR2 rescued the expression of β-catenin, which was suppressed by EGFR inhibitor AG1478 indicating an alternative pathway to regulate β-catenin independent of EGFR signal. These effects were abolished when a monoclonal antibody against AGR2 was added to the experiments, confirming the effects are caused by AGR2 only. Putting together, our results show that extracellular AGR2 signaling pathway involves endocytosis mediated cellular translocation, direct binding and regulating β-catenin nuclear accumulation. It is also a target against tumor initiated AGR2 signaling to form and maintain tumor microenvironment.

Discovery of fibrillar adhesins across bacterial species

BackgroundFibrillar adhesins are long multidomain proteins that form filamentous structures at the cell surface of bacteria. They are an important yet understudied class of proteins composed of adhesive and stalk domains that mediate interactions of bacteria with their environment. This study aims to characterize fibrillar adhesins in a wide range of bacterial phyla and to identify new fibrillar adhesin-like proteins to improve our understanding of host-bacteria interactions.ResultsThrough careful literature and computational searches, we identified 82 stalk and 27 adhesive domain families in fibrillar adhesins. Based on the presence of these domains in the UniProt Reference Proteomes database, we identified and analysed 3,542 fibrillar adhesin-like proteins across species of the most common bacterial phyla. We further enumerate the adhesive and stalk domain combinations found in nature and demonstrate that fibrillar adhesins have complex and variable domain architectures, which differ across species. By analysing the domain architecture of fibrillar adhesins, we show that in Gram positive bacteria, adhesive domains are mostly positioned at the N-terminus and cell surface anchors at the C-terminus of the protein, while their positions are more variable in Gram negative bacteria. We provide an open repository of fibrillar adhesin-like proteins and domains to enable further studies of this class of bacterial surface proteins.ConclusionThis study provides a domain-based characterization of fibrillar adhesins and demonstrates that they are widely found in species across the main bacterial phyla. We have discovered numerous novel fibrillar adhesins and improved our understanding of pathogenic adhesion and invasion mechanisms.

Biomimetic recognition strategy for efficient capture and release of circulating tumor cells.

Efficient capture and release of circulating tumor cells play an important role in cancer diagnosis, but the limited affinity of monovalent adhesion molecules in existing capture technologies leads to low capture efficiency, and the captured cells are difficult to be separated. Inspired by the phenomenon that the long tentacles of jellyfish contain multiple adhesion domains and can effectively capture moving food, we have constructed a biomimetic recognition strategy to capture and release tumor cells. In details, gold-coated magnetic nanomaterials (Au@Fe3O4 NPs) were first prepared and characterized by scanning electron microscopy, UV-vis absorption spectra, and Zeta potential. Then, the DNA primers modified on Au@Fe3O4 nanoparticles can be extended to form many radialized DNA products by rolling circle amplification. These long DNA products resemble jellyfish tentacles and contain multivalent aptamers that can be extended into three dimensions to increase the accessibility of target cells, resulting in efficient, simple, rapid, and specific cells capture. The capture efficiencies are no less than 92% in PBS buffer and 77% in blood. Subsequently, DNase I was selected to degrade biomimetic tentacles to release the captured tumor cells with high viability. This release strategy can not only improve cell viability, but also reduce a tedious release process and unnecessary costs. We believe that the proposed method can be expanded for the capture and release of various tumor cells and will inspire the development of circulating tumor cells analysis. A biomimetic recognition strategy for capture and release of circulating tumor cells has been developed. This method modified specific P1 DNA primers on Au@Fe3O4 NPs to form many radialized DNA products by rolling circle amplification. These products can efficiently capture CTCs since it contains multiple aptamers with a multivalent binding capacity. This make it a promising tool to capture and release of other tumor cells, and will inspire the development of CTC analysis.

Platelet derived growth factor receptor \u03b2 (PDGFR\u03b2) is a host receptor for the human malaria parasite adhesin TRAP

Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.

Individuality, self and sociality of vascular plants

Vascular plants are integrated into coherent bodies via plant-specific synaptic adhesion domains, action potentials (APs) and other means of long-distance signalling running throughout the plant bodies. Plant-specific synapses and APs are proposed to allow plants to generate their self identities having unique ways of sensing and acting as agents with their own goals guiding their future activities. Plants move their organs with a purpose and with obvious awareness of their surroundings and require APs to perform and control these movements. Self-identities allow vascular plants to act as individuals enjoying sociality via their self/non-self-recognition and kin recognition. Flowering plants emerge as cognitive and intelligent organisms when the major strategy is to attract and control their animal pollinators as well as seed dispersers by providing them with food enriched with nutritive and manipulative/addictive compounds. Their goal in interactions with animals is manipulation for reproduction, dispersal and defence. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.