Protein Adsorption Research Articles

Effect of hydroxy-PEO chain density and uremic toxins on plasma protein adsorption

Protein adsorption influences the host response to blood contacting biomaterials. End-tethered polyethylene oxide (PEO) is a gold-standard film for reducing non-specific protein adsorption at the blood-material interface. That said, almost all protein adsorption studies utilize blood from healthy donors, whereas blood composition can vary greatly depending on the disease. Kidney failure leads to the dramatic retention of small molecules (i.e., uremic toxins) within the blood compartment, and their effect on the inhibition of protein adsorption to PEO films is unknown. To understand the effect these uremic toxins have on protein adsorption, surfaces with different chain densities of end-tethered hydroxy-PEO were incubated in platelet-poor plasma laden with uremic toxins. PEO films were characterized using dynamic contact angles and X-ray photoelectron spectroscopy. PEO chain densities were verified using spectroscopic ellipsometry. Eluted proteins were characterized using immunoblot techniques. It was observed that PEO chain density and uremic toxins affected the amount of individually adsorbed proteins and the relative composition of the adsorbed protein corona; especially albumin, complement C3, factor XI, and fibrinogen. This knowledge is considered crucial to the advancement of surfaces for a personalized approach to treating patients with kidney failure.

Temperature dependent human serum albumin Corona formation: A case study on gold nanorods and nanospheres.

Protein molecules interact with nanoparticles to form a protein layer on the surface called the protein corona. Corona formation can be affected by the temperature and shape of the nanoparticles thereby impacting the fate of the nanoparticles inside physiological systems. We have investigated the human serum albumin (HSA) corona formation and its interactions with gold nanospheres and nanorods at different temperatures (18-42°C). UV-Vis, fluorescence, isothermal titration calorimetry (ITC), x-ray photoelectron spectroscopy (XPS) and circular dichroism (CD) experiments have been performed to determine the changes due to the shape and temperature. UV-Vis spectra show a greater propensity of corona induced aggregation in the nanorods compared to the nanospheres. The Stern-Volmer plot indicates that static quenching is predominant in the HSA-AuNP interactions with higher quenching efficiency for nanorods than nanospheres. ITC analyses show that HSA-nanorods are involved in more favorable interactions compared to HSA-nanospheres. XPS studies indicate a more electron rich environment on the AuNRs surface and higher AuS interactions in AuNSs. CD spectra show higher secondary structural changes with temperature in case of HSA-AuNR interactions compared to HSA-AuNS interactions. The changes in the protein corona due to nanoparticle shape and variable temperature have been investigated through protein adsorption and composition, types of interactions and protein conformation.

PH-dependent emulsifying properties of pea protein isolate: Investigation of the structure - Function relationship.

This study investigated the relationship between pea protein isolates (PPI) emulsifying properties and their structural, interfacial, and physicochemical characteristics at various pH values (native pH, 7, 5, and 3). Emulsion characteristics including emulsifying activity and stability, droplet size, flocculation index (FI) and coalescence index (CI) were examined. Additionally, physicochemical properties such as solubility, zeta potential, surface hydrophobicity, interfacial protein adsorption and protein conformation were analyzed. Results revealed significant pH-dependent variations in emulsifying performance. The poorest emulsifying performance was observed at pH5, with the largest droplet size (28.84μm) and highest CI (38.94%). Optimal emulsifying properties were noticed at native pH, with the smallest droplet size (7.73μm) and lowest CI (4.69). At pH3, good emulsifying ability with the highest physical stability (5.43) were observed, associated with increased surface hydrophobicity and the presence of some aggregates contributing to the formation of cohesive interfacial film. Structural elements, particularly β-sheets and random coils, were positively correlated with emulsifying activity and stability, while β-turns had a negative impact. These findings provide insights into the pH-dependent emulsifying behavior of PPI, highlighting the complex relationship between protein structure and functionality, enabling the optimization of the use of PPI as an emulsifier in food applications.

Synthesis and characterization of TiO2-ZnO composite thin films for biomedical applications.

Titania (TiO2) has superior biocompatibility, while zinc oxide (ZnO) is antibacterial. This investigation aimed to study the influence of TiO2-ZnO composite films on enhancing the biocompatibility of stainless steel (SS). Radio-frequency magnetron sputtering (RF-MS) technique is used to synthesize TiO2-ZnO composite thin films on 304-SS substrates from three sputtering targets with typical chemical compositions of 100% TiO2, 90%TiO2-10%ZnO, and 75%TiO2-25%ZnO, mixed by their respective weight percentages. The influence of surface chemistry, morphology, and wettability of TiO2-ZnO composite film on its osseointegration and antifouling characteristics was studied. The biocompatibility was assessed by protein adsorption kit, cytotoxicity assay, and cell adhesion of MG63 osteoblast cells, followed by S. aureus bacterial adhesion studies. All RF-MS films displayed hydrophobicity, minimal bacterial-cell adhesion, and higher cytocompatibility than the SS. RF-MS films deposited from the 75%TiO2-25%ZnO target exhibited the highest antifouling capability due to the least protein adsorption and the highest antibacterial ZnO concentration. However, increased ZnO concentration decreased MG63 cell viability. RF-MS films deposited from the 90%TiO2-10%ZnO target showed the highest mammalian cell viability of ≈88% and attachment. High plasma protein adsorption caused decreased mammalian cell viability and higher bacterial adhesion on 100% TiO2film and SS. Biocompatible and antifouling TiO2-ZnO composite thin films on SS substrates offer an alternative to conventional antibiotic coatings to combat antimicrobial resistance (AMR) and biofilm-related infections.

Effects of Chemical Pretreatments of Wood Cellulose Nanofibrils on Protein Adsorption and Biological Outcomes.

Wood-based nanocellulose is emerging as a promising nanomaterial in the field of tissue engineering due to its unique properties and versatile applications. Previously, we used TEMPO-mediated oxidation (TO) and carboxymethylation (CM) as chemical pretreatments prior to mechanical fibrillation of wood-based cellulose nanofibrils (CNFs) to produce scaffolds with different surface chemistries. The aim of the current study was to evaluate the effects of these chemical pretreatments on serum protein adsorption on 2D and 3D configurations of TO-CNF and CM-CNF and then to investigate their effects on cell adhesion, spreading, inflammatory mediator production in vitro, and the development of foreign body reaction (FBR) in vivo. Mass spectrometry analysis revealed that the surface chemistry played a key role in determining the proteomic profile and significantly influenced the behavior of periodontal ligament fibroblasts and osteoblast-like cells (Saos-2). The surface of TO-CNF 2D samples showed the highest protein adsorption followed by TO-CNF 3D samples. CM-CNF 2D samples adsorbed a higher number of proteins than their 3D counterparts. None of the CNF scaffolds showed toxicity in vitro or in vivo. However, carboxymethylation pretreatment negatively affected the adhesion, morphology, and spreading of both cell types. Although the CNF materials displayed clear differences in surface chemistry and proteomic profiles, both triggered the same foreign body response after being subcutaneously implanted in rats for 90 days. This observation highlights that the degradation rate of CNF scaffolds plays a central role in maintaining the foreign body response in vivo. It is imperative to comprehend the impact of chemical pretreatments of CNFs on protein adsorption and their interaction with diverse host cell types prior to the investigation of potential modifications. This knowledge is indispensable for the advancement of CNFs in regenerative applications within tissue engineering.

Zwitterionic Hydrogels: From Synthetic Design to Biomedical Applications.

Zwitterionic hydrogels have emerged as a highly promising class of biomaterials, attracting considerable attention due to their unique properties and diverse biomedical applications. Zwitterionic moieties, with their balanced positive and negative charges, endow hydrogels with exceptional hydration, resistance to nonspecific protein adsorption, and low immunogenicity due to their distinctive molecular structure. These properties facilitate various biomedical applications, such as medical device coatings, tissue engineering, drug delivery, and biosensing. This review explores the structure-property relationships in zwitterionic hydrogels, highlighting recent advances in their design principles, synthesis methods, structural characteristics, and biomedical applications. To meet the evolving and growing demand for the biomedical field, this review examines current challenges and explores future research directions for optimizing the multifunctional properties of zwitterionic hydrogels. As promising candidates for advanced biomaterials, zwitterionic hydrogels are poised to address critical challenges in biomedical applications, paving the way for improved therapeutic outcomes and broader applicability in healthcare.

Sequential Growth of Quantized Peptide Brushes on Colloidal Gold.

We synthesized rigid, macromolecular brushes with well-defined and quantized brush lengths on a gold nanoparticle substrate by using a macromolecular "grafting from" approach. The macromonomers used in these brushes were thiol- and maleimide-functionalized peptide coiled coil "bundlemers" that fold into discrete 4 nm × 2 nm (length × diameter) cylindrical nanoparticles. With each added peptide macromonomer layer, brush thickness increased by approximately the length of a single bundlemer nanoparticle. Due to the quantized nature of these brushes, we were able to determine grafting density and brush thickness through a simplified local surface plasmon resonance model (LSPR). The accuracy of this model is validated by dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryoTEM). The high grafting density and precise brush thickness, demonstrated by the sequential macromolecular growth of these brushes, could lead to the development of better multifunctional LSPR-based biosensors. Additionally, the LSPR model developed in this paper could be modified to describe other peptides and proteins and could prove to be a valuable tool for characterizing protein adsorption on metallic nanoparticles.

Unraveling the mystery: effect of trapped air on platelet adhesion on hydrophobic nanostructured titanium dioxide.

Nature-inspired superhydrophobic materials have attracted considerable interest in blood-contacting biomedical applications due to their remarkable water-repellent and self-cleaning properties. However, the interaction mechanism between blood components and superhydrophobic surfaces remains unclear. To explore the effect of trapped air on platelet adhesion, we designed four distinct hydrophobic titanium dioxide (TiO2) nanostructures with different fractions of trapped air. Ultrasonication was used to remove trapped air, allowing for direct comparison between hydrophobic surfaces with and without observable trapped air. The results demonstrate that all four kinds of hydrophobic materials significantly reduce platelet adhesion, regardless of observable trapped air. As nanostructure size increases, the proportion of air also increases, trapped air reduces fibrinogen adsorption but increases platelet adhesion, particularly in the largest nanostructures with superhydrophobicity. Upon air removal, protein adsorption increases compared to the same sample with air, while platelet adhesion decreases. This indicates that trapped air reduces protein adsorption but unexpectedly enhances platelet adhesion, which is contrary to our intuitive expectations. Conversely, hydrophobic surfaces without trapped air minimize platelet adhesion. To gain a better understanding of this phenomenon, we propose an interpretable model. Overall, this study challenges conventional assumptions and offers new insights for the design and application of superhydrophobic materials.

Plasmonic Slippery Surface for Surface-Enhanced Raman Spectroscopy and Protein Adsorption Inhibition.

Slippery liquid-infused porous surfaces (SLIPSs) are a class of surface that offers low contact angle hysteresis and low tilt angle for water droplet shedding. This property also endows the surface with pinning-free evaporation, which in turn has been exploited for analyte concentration enrichment for Surface Enhanced Raman Spectroscopic applications and antibiofouling. Herein, we demonstrate a facile approach for creating SLIPS with low contact angle hysteresis and low tilt angle for water shedding by coating the equal-volume mixture of polydimethylsiloxane (PDMS) and silicone oil. By exploiting the in situ plasmonic particle reduction capability of the PDMS, the surface is converted to plasmonic SLIPS, which illustrates its potential as a sensitive analytical platform via surface-enhanced Raman spectroscopy. The Raman spectroscopic studies using crystal violet as a reference sample show a limit of detection of 76 pM. Further, we have demonstrated that the fabricated plasmonic substrate is found to be more efficient in inhibiting proteins (bovine serum albumin) on the surface compared to pristine PDMS surfaces. Our fabricated plasmonic surface can find applications in ultrasensitive molecular detection for applications related to analytical chemistry, diagnostics, environmental monitoring, and national security and more importantly can control the nonspecific adsorption of proteins.

Machine learning models for predicting interaction affinity energy between human serum proteins and hemodialysis membrane materials

Membrane incompatibility poses significant health risks, including severe complications and potential fatality. Surface modification of membranes has emerged as a pivotal technology in the membrane industry, aiming to improve the hemocompatibility and performance of dialysis membranes by mitigating undesired membrane-protein interactions, which can lead to fouling and subsequent protein adsorption. Affinity energy, defined as the strength of interaction between membranes and human serum proteins, plays a crucial role in assessing membrane-protein interactions. These interactions may trigger adverse reactions, potentially harmful to patients. Researchers often rely on trial-and-error approaches to enhance membrane hemocompatibility by reducing these interactions. This study focuses on developing machine learning algorithms that accurately and rapidly predict affinity energy between novel chemical structures of membrane materials and human serum proteins, based on a molecular docking dataset. Various membrane materials with distinct characteristics, chemistry, and orientation are considered in conjunction with different proteins. A comparative analysis of linear regression, K-nearest neighbors regression, decision tree regression, random forest regression, XGBoost regression, lasso regression, and support vector regression is conducted to predict affinity energy. The dataset, comprising 916 records for both training and test segments, incorporates 12 parameters extracted from data points and involves six different proteins. Results indicate that random forest (R² = 0.8987, MSE = 0.36, MAE = 0.45) and XGBoost (R² = 0.83, MSE = 0.49, MAE = 0.49) exhibit comparable predictive performance on the training dataset. However, random forest outperforms XGBoost on the testing dataset. Seven machine learning algorithms for predicting affinity energy are analyzed and compared, with random forest demonstrating superior predictive accuracy. The application of machine learning in predicting affinity energy holds significant promise for researchers and professionals in hemodialysis. These models, by enabling early interventions in hemodialysis membranes, could enhance patient safety and optimize the care of hemodialysis patients.

Antifouling Zwitterionic Polymer Coatings for Blood-Bearing Medical Devices.

Blood-bearing medical devices are essential for the delivery of critical care medicine and are often required to function for weeks to months. However, thrombus formation on their surfaces can lead to reduced device function and failure and expose patients to systemic thrombosis risks. While clinical anticoagulants reduce device related thrombosis, they also increase patient bleeding risk. The root cause of device thrombosis and inflammation is protein adsorption on the biomaterial surfaces of these devices. Protein adsorption activates the coagulation cascade and complement, and this, in turn, activates platelets and white blood cells. Surface modifications with zwitterionic polymers are particularly effective at reducing protein adsorption as well as conformational changes in proteins due to their hydrophilicity. Multiple coating strategies have been developed using carboxybetaine (CB), sulfobetaine (SB), and 2-methacryloyloxyethyl phosphorylcholine (MPC) zwitterionic polymers applied to the metals and hydrophobic polymers that make up the bulk of blood-bearing medical devices. These coatings have been highly successful at creating large reductions in protein adsorption and platelet adhesion during studies on the order of hours on flat surfaces and at reducing thrombus formation for up to a few days in full medical devices. Future work needs to focus on their ability to limit inflammation, particularly during hemodialysis, and in providing anticoagulation on the order of weeks, particularly in artificial lungs.

One-Step Synthesis of Carboxylated Polyethylene Glycol-Modified Polystyrene Microspheres and Their Application in the Luminescent Oxygen Channel Immunoassay.

As one of the key diagnostic methods for detecting biomarkers and antigen-antibody interactions, the luminescent oxygen channel immunoassay (LOCI) has been widely applied in bioanalysis and other fields. In the context of LOCI, the performance of the prepared donor polystyrene (PS) microspheres significantly impacts the detection signal values. In this study, an attempt was made to synthesize PS microspheres via one-step polymerization of styrene with an amphiphilic monomer (PEOOH), followed by swelling the silicon phthalocyanine photosensitizer into the PS microspheres, resulting in the functionalization of the PS microspheres with polyethylene glycol segments. The chemical stability and water solubility of polyethylene glycol (PEG) make it a versatile surface modification material while also inhibiting nonspecific protein adsorption. Results indicated that with increasing PEOOH content, the nonspecific protein adsorption of the resulting PS microspheres reduced, with the adsorption ability for BSA decreasing from 26.8 to 1.3 mg/g, approximately decreasing by 95.2%. Furthermore, the results demonstrated that PS microspheres prepared with 6% PEOOH exhibited a maximum signal-to-noise ratio (S/N) (approximately 28.7), nearly 14 times higher than PS microspheres without PEOOH (approximately 2.1). The analytical performance of the system for detecting staphylococcal enterotoxin B (SEB) revealed a detection limit of 0.1 ng/mL and a linear concentration range of 0.1 to 50 ng/mL for the donor PS microspheres (6% PEOOH). The synthesized donor PS microspheres exhibit a uniform particle size and stable signals, making them effective LOCI microcarriers. These properties facilitate a deeper understanding of molecular interactions and signal transduction mechanisms within biological systems.

Depolarized Forward Light Scattering for Subnanometer Precision in Biomolecular Layer Analysis on Gold Nanorods.

Functional gold nanoparticles have emerged as a cornerstone in targeted drug delivery, imaging, and biosensing. Their stability, distribution, and overall performance in biological systems are largely determined by their interactions with molecules in biological fluids as well as the biomolecular layers they acquire in complex environments. However, real-time tracking of how biomolecules attach to colloidal nanoparticles, a critical aspect for optimizing nanoparticle function, has proven to be experimentally challenging. To address this issue, we present a depolarized forward light scattering (DFLS) method that measures rotational relaxation constants. In DFLS, optically anisotropic nanoparticles are illuminated with linearly polarized light and the forward light scattering is analyzed in a cross-polarized configuration. We demonstrate the application of DFLS to characterize various functional coatings, analyze biomolecular binding kinetics to gold nanoparticles, and determine specific protein adsorption affinity constants. Our results indicate that DFLS offers a powerful approach to studying nanoparticle-biomolecule interactions in complex environments such as bodily fluids, thereby opening new pathways for advancements in nanomedicine and the optimization of nanoparticle-based drug delivery systems.

Biocompatible EDOT-Pyrrole Conjugated Conductive Polymer Coating for Augmenting Cell Attachment, Activity, and Differentiation.

Developing scaffolds supporting functional cell attachment and tissue growth is critical in basic cell research, tissue engineering, and regenerative medicine approaches. Though poly(ethylene glycol) (PEG) and its derivatives are attractive for hydrogels and scaffold fabrication, they often require bioactive modifications due to their bioinert nature. In this work, biomimetic synthesized conductive polypyrrole-poly(3,4-ethylenedioxythiophene) copolymer doped with poly(styrenesulfonate) (PPy-PEDOT:PSS) was used as a biocompatible coating for poly(ethylene glycol) diacrylate (PEGDA) hydrogel to support neuronal and muscle cells' attachment, activity, and differentiation. The synthesized copolymer was characterized by Raman spectroscopy and dynamic light scattering. Its electrochemical properties were studied using galvanostatic charge-discharge (GCD) and voltammetry. PPy-PEDOT:PSS-coated hydrogels were characterized by Raman spectroscopy and atomic force microscopy, and protein adsorption was assessed using a quartz crystal microbalance with dissipation monitoring. Attachment and differentiation of the ND7/23 neuron hybrid cell line and C2C12 myoblasts were evaluated by cell cytoskeleton staining and quantification of morphological parameters. Viability was assessed by live/dead staining using flow cytometry. Cortex neural activity was studied by calcium ion influx that could be detected through the dynamic fluorescence changes of Fluo-4. The PPy-PEDOT:PSS coating supported cell attachment and differentiation and was nontoxic to cells. Primary neurons attached and remained responsive to electrical stimulation. Altogether, the biocompatible copolymer PPy-PEDOT:PSS is a simple yet effective alternative for hydrogel coating and presents great potential as an interface for nervous and other electrically excitable tissues.

Autonomous Anticoagulation on a Biomimetic Al-Based Hierarchical Surface.

Studies targeting the blood repellency and autonomous anticoagulation of superhydrophobic (SH) surfaces are potentially valuable for their application in blood contact. The anticoagulation abilities and potential mechanisms of different SH surfaces urgently need to be revealed. In this study, a range of microprotrusion arrays on Al substrates with varying spacings via laser ablation through the utilization of organic adsorption and siloxane coupling reactions were fabricated. Consequently, gridded SH Al-based surfaces were prepared, and their blood-repellency and autonomous anticoagulation properties were evaluated. In vitro experiments demonstrated the effectiveness of these surfaces in preventing nonspecific protein adsorption and platelet adhesion, and the surfaces exhibited no indications of hemolysis or toxicity. Remarkably, the SH surfaces maintained good antiplatelet adhesion and platelet activation inhibition properties after 7 days of incubation in platelet-rich plasma, and the anticoagulation capacity of different SH surfaces was compared with elements analysis on the surfaces. Specifically, the SH Al surface exhibited low protein adsorption when incubated with 10 mg/mL of bovine serum albumin solution. Furthermore, this study illustrated the relationship between the hierarchical micronano structure of the SH surfaces and their autonomous anticoagulant behavior. The integration of a readily available SH surface with autonomous anticoagulant ability represents a promising strategy for the application of metallic materials in medical devices involving blood contact.

Adsorption Force of Fibronectin Regulates Protein Reorganization, Desorption, and Endocytosis.

Protein adsorption on biomaterials occurs before cell adhesion. To adapt the properties of biomaterials, adhered cells may utilize and modify adsorbed proteins for survival and function. In this process, the protein-material interfacial force (Fad) is supposed to play vital roles, which, however, has received little attention. Here, we found that rat mesenchymal stem cells (rMSCs) can utilize the adsorbed fibronectin (FN) via reorganization, desorption, or endocytosis, and these utilization processes are regulated by Fad through regulating cell adhesion and force balance between the cell traction force and Fad. Furthermore, protein utilization has an Fad-dependent temporal sequence. On low Fad surface, FN endocytosis might happen prior to FN desorption and aggregation. This work confirms the importance of Fad in protein utilization and provides new insight into the mechanism by which cells process their surrounding ECM proteins, which may help to guide the design of better biomaterials.

Effect of bioactive Rosa roxburghii Tratt fruit polysaccharide on the structure and emulsifying property of lactoferrin protein.

Lactoferrin protein (LF) is a natural protein with certain emulsifying ability, but is sensitive to be affected by environmental factors and has poor oxidative stability to be used as emulsifier. In this study, the emulsifying ability of LF was significantly improved after conjugation with Rosa roxburghii Tratt fruit polysaccharides (RTFP), and the emulsion stability mechanism of LF-RTFP conjugates (L-R) were elucidated through the utilization of CLSM (confocal laser scanning microscopy), interfacial tension, apparent viscosity, and protein adsorption rate. The emulsion stabilized by L-R showed the smaller particle size (17.17 ± 0.13 μm), which reduced by 51 % compared with that of LF. After conjugation with RTFP, the hydrophobic amino acids that are originally inside the structure of LF would be exposed on the protein surface. In addition, the protein adsorption rate of L-R stabilized emulsion interface was 62.70 ± 0.71 %, 2.4 times higher than that of LF. The optical microscopy and CLSM experiments indicated that the glycosylation with RTFP increased the bridged flocculation and further formed gel network structure in the emulsion stabilized by LF. These findings suggested that the novel emulsifier prepared by the Maillard reaction between LF and RTFP showed potential to stable emulsion.

Hybrid Bilayer Interfaces within Reversed-Phase Chromatographic Silica Formed by Self-Assembly of Long-Chain Primary Alcohols.

Modification of silica interfaces by covalent attachment of functional ligands is a primary means of controlling the interfacial chemistry of porous silicas used in separations, environmental cleanup, and biosensing. Recently, modification of hydrophobic, n-alkyl-silane-functionalized interfaces has been achieved through self-assembly of zwitterionic phospholipids or mixed-charged surfactants to form "hybrid bilayers", producing interfaces that mimic lipid-bilayer partitioning and provide shape-selective partitioning of aromatic hydrocarbons. Charged headgroups, however, introduce electrostatic interactions that strongly influence the retention of ionizable solutes and require careful control over pH and ionic strength in the solution phase. In this work, we propose modification of C18-functionalized chromatographic silica surfaces through self-assembly of long-chain primary alcohols to form uncharged hybrid-bilayer surfaces. Hybrid bilayers formed from alcohols ranging from C12OH to C22OH are investigated with in situ confocal-Raman microscopy, and the spectra indicate that they form highly ordered n-alkane structures, with order increasing as a function of alcohol chain length. Temperature-dependent Raman spectra of C12OH-C22OH hybrid bilayers were collected to investigate their melting transitions. Multivariate curve resolution of these spectra show broad, two-component melting transitions, indicating alcohol and C18 alkyl chains melt simultaneously. These results suggest an interdigitated interfacial structure, where the hydrocarbon chains of the adsorbed alcohol extend into the underlying C18 chains, ordering both layers. Interdigitation is confirmed by a temperature-dependent study of a deuterated C16-OH bilayer, where spectrally resolved Raman bands from deuterated and protiated hydrocarbons melt together. Finally, n-alkyl alcohol bilayers were tested for protein repellency, where no protein adsorption was observed when equilibrated with ∼1 mg/mL bovine serum albumin. Bilayers C16OH in chain length are shelf stable at refrigerated temperatures for months. These results demonstrate long-chain alcohol bilayers can be utilized to control the interfacial hydrocarbon structure of C18-modified silica and have potential for use in separations, biosensing, and anti-biofouling applications.

Zwitterionic Poly(ethylene glycol) Nanoparticles Minimize Protein Adsorption and Immunogenicity for Improved Biological Fate.

We report the assembly of poly(ethylene glycol) nanoparticles (PEG NPs) and optimize their surface chemistry to minimize the formation of protein coronas and immunogenicity for improved biodistribution. PEG NPs cross-linked with disulfide bonds are synthesized utilizing zeolitic imidazolate framework-8 NPs as the templates, which are subsequently modified with PEG molecules with different end groups (carboxyl, methoxy, or amino) to vary the surface chemistry. Among the modifications, the amino and residual carboxyl groups form a pair of zwitterionic structures on the surface of PEG NPs, which minimize the adsorption of proteins (e.g., immunoglobulin, complement proteins) and maximize the blood circulation time. The influence of preexisting PEG antibodies in mice on the pharmacokinetics of zwitterionic PEG NPs is negligible, which demonstrates the resistance of anti-PEG antibodies and inhibition of the accelerated blood clearance phenomenon. This research highlights the importance of the surface chemistry of PEGylated NPs in the design of delivery systems and reveals their translational potential for cancer therapy.

Prof. George Whitesides’ Contributions to Self-Assembled Monolayers (SAMs): Advancing Biointerface Science and Beyond

Prof. George Whitesides’ pioneering contributions to the field of self-assembled monolayers (SAMs) have profoundly influenced biointerface science and beyond. This review explores the development of SAMs as highly organized molecular structures, focusing on their role in advancing surface science, biointerface research, and biomedical applications. Prof. Whitesides’ systematic investigations into the effects of SAMs’ terminal group chemistries on protein adsorption and cell behavior culminated in formulating “Whitesides’ Rules”, which provide essential guidelines for designing bioinert surfaces. These principles have driven innovations in anti-fouling coatings for medical devices, diagnostics, and other biotechnological applications. We also discuss the critical role of interfacial water in SAM bioinertness, with studies demonstrating its function as a physical barrier preventing protein and cell adhesion. Furthermore, this review highlights how data science and machine learning have expanded the scope of SAM research, enabling predictive models for bioinert surface design. Remarkably, Whitesides’ Rules have proven applicable not only to SAMs but also to polymer-brush films, illustrating their broad relevance. Prof. Whitesides’ work provides a framework for interdisciplinary advancements in material science, bioengineering, and beyond. The enduring legacy of his contributions continues to inspire innovative approaches to addressing challenges in biomedicine and biotechnology.