Cellular Deformation Research Articles

Superior strength-ductility synergy in additively manufactured CoCrFeNi high-entropy alloys with multi-scale hierarchical microstructure

Additive manufacturing offers a feasible route for fabricating net-shape metallic materials with advanced physicochemical and mechanical properties, which is unattainable through conventional routes. This study focuses on the processing parameters, microstructural, and mechanical properties of the CoCrFeNi high-entropy alloys (HEAs) fabricated via laser powder bed fusion (LPBF). A near-dense LPBF CoCrFeNi HEA was manufactured by fine-tuning the parameters. Compared with conventionally processed CoCrFeNi HEAs, the as-built samples exhibit excellent strength-ductility synergy with 200 % higher yield strength and unsacrificed ductility. Microstructural analyses of the LPBF samples demonstrate a hierarchical structure including melt pools, columnar grains, dislocation cells, and elemental segregations. This excellent strength is attributed to the high-density dislocation cellular structure and Cr2O3 nanoparticles that impede the dislocation motion. The excellent ductility correlates to the steady work-hardening regulated by the interactions between cellular structure, dislocations, deformation twins, and nanoprecipitation. This work provides promising outlook towards fabricating high-performance alloys with tailored hierarchical microstructure.

Compressible Hollow Microlasers in Organoids for High-Throughput and Real-Time Mechanical Screening.

Mechanical stress within organoids is a pivotal indicator in disease modeling and pharmacokinetics, yet current tools lack the ability to rapidly and dynamically screen these mechanics. Here, we introduce biocompatible and compressible hollow microlasers that realize all-optical assessment of cellular stress within organoids. The laser spectroscopy yields identification of cellular deformation at the nanometer scale, corresponding to tens of pascals stress sensitivity. The compressibility enables the investigation of the isotropic component, which is the fundamental mechanics of multicellular models. By integrating with a microwell array, we demonstrate the high-throughput screening of mechanical cues in tumoroids, establishing a platform for mechano-responsive drug screening. Furthermore, we showcase the monitoring and mapping of dynamic contractile stress within human embryonic stem cell-derived cardiac organoids, revealing the internal mechanical inhomogeneity within a single organoid. This method eliminates time-consuming scanning and sample damage, providing insights into organoid mechanobiology.

Matricellular protein CCN1 promotes collagen alignment and scar integrity after myocardial infarction

BackgroundMembers of the cellular communication network family (CCN) of matricellular proteins, like CCN1, have long been implicated in the regulation of cellular processes underlying wound healing, tissue fibrogenesis, and collagen dynamics. While many studies suggest antifibrotic actions for CCN1 in the adult heart through the promotion of myofibroblast senescence, they largely relied on exogenous supplementation strategies in in vivo models of cardiac injury where its expression is already induced—which may confound interpretation of its function in this process. The objective of this study was to interrogate the role of the endogenous protein on fibroblast function, collagen structural dynamics, and its associated impact on cardiac fibrosis after myocardial infarction (MI). Methods/resultsHere, we employed CCN1 loss-of-function methodologies, including both in vitro siRNA-mediated depletion and in vivo fibroblast-specific knockout mice to assess the role of the endogenous protein on cardiac fibroblast fibrotic signaling, and its involvement in acute scar formation after MI. In vitro depletion of CCN1 reduced cardiac fibroblast senescence and proliferation. Although depletion of CCN1 decreased the expression of collagen processing and stabilization enzymes (i.e., P4HA1, PLOD1, and PLOD2), it did not inhibit myofibroblast induction or type I collagen synthesis. Alone, fibroblast-specific removal of CCN1 did not negatively impact ventricular performance or myocardial collagen content but did contribute to disorganization of collagen fibrils and increased matrix compliance. Similarly, Ccn1 ablated animals subjected to MI showed no discernible alterations in cardiac structure or function one week after permanent coronary artery ligation, but exhibited marked increases in incidence of mortality and cardiac rupture. Consistent with our findings that CCN1 depletion does not assuage myofibroblast conversion or type I collagen synthesis in vitro, Ccn1 knockout animals revealed no measurable differences in collagen scar width or mass compared to controls; however, detailed structural analyses via SHG and TEM of scar regions revealed marked alterations in their scar collagen topography—exhibiting changes in numerous macro- and micro-level collagen architectural attributes. Specifically, Ccn1 knockout mice displayed heightened ECM structural complexity in post-MI scar regions, including diminished local alignment and heightened tortuosity of collagen fibers, as well as reduced organizational coherency, packing, and size of collagen fibrils. Associated with these changes in ECM topography with the loss of CCN1 were reductions in fibroblast-matrix interactions, as evidenced by reduced fibroblast nuclear and cellular deformation in vivo and reduced focal-adhesion formation in vitro; findings that ultimately suggest CCN1’s ability to influence fibroblast-led collagen alignment may in part be credited to its capacity to augment fibroblast-matrix interactions. ConclusionsThese findings underscore the pivotal role of endogenous CCN1 in the scar formation process occurring after MI, directing the appropriate arrangement of the extracellular matrix's collagenous components in the maturing scar—shaping the mechanical properties that support its structural stability. While this suggests an adaptive role for CCN1 in regulating collagen structural attributes crucial for supporting scar integrity post MI, the long-term protracted expression of CCN1 holds maladaptive implications, potentially diminishing collagen structural complexity and compliance in non-infarct regions.

Engineering the Cellular Microenvironment: Integrating Three-Dimensional Nontopographical and Two-Dimensional Biochemical Cues for Precise Control of Cellular Behavior.

The development of biomaterials capable of regulating cellular processes and guiding cell fate decisions has broad implications in tissue engineering, regenerative medicine, and cell-based assays for drug development and disease modeling. Recent studies have shown that three-dimensional (3D) nanoscale physical cues such as nanotopography can modulate various cellular processes like adhesion and endocytosis by inducing nanoscale curvature on the plasma and nuclear membranes. Two-dimensional (2D) biochemical cues such as protein micropatterns can also regulate cell function and fate by controlling cellular geometries. Development of biomaterials with precise control over nanoscale physical and biochemical cues can significantly influence programming cell function and fate. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate the precise engineering of single cell architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between the nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, our results suggest that cell elongation on nanopillars enhances nanopillar-induced endocytosis. We believe our platform serves as a versatile tool for further explorations into programming cell function and fate through combined physical cues that create nanoscale curvature on cell membranes and biochemical cues that control the geometry of the cell.

Tunneling nanotubes mediate KRas transport: Inducing tumor heterogeneity and altering cellular membrane mechanical properties

Mutation in oncogene KRas plays a crucial role in the occurrence and progression of numerous malignant tumors. Malignancy involves changes in cell mechanics for extensive cellular deformation during metastatic dissemination. We hypothesize that oncogene KRas mutations are intrinsic to alterations in cellular mechanics that promote malignant tumor generation and progression. Here, we demonstrate the use of optical tweezers coupled with a confocal fluorescence imaging system and gene interference technique to reveal that the mutant KRas protein can be transported between homogeneous and heterogeneous tumor cells by tunneling nanotubes (TNTs), resulting in a significant reduction of membrane tension and acceleration of membrane phospholipid flow in the recipient cells. Simultaneously, the changes in membrane mechanical properties of the tumor cells also enhance the metastatic and invasive ability of the tumors, which further contribute to the deterioration of the tumors. This finding helps to clarify the association between oncogene mutations and changes in the mechanical properties of tumor cells, which provides a theoretical basis for the development of cancer treatment strategies. Statement of significanceHere, we present a laser confocal fluorescence system integrated with optical tweezers to observe the transfer of mutant KRasG12D protein from mutant cells to wild-type cells through TNTs. Malignancy involves changes in cell mechanics for extensive cellular deformation during metastatic dissemination. Our results demonstrate a significant decrease in membrane tension and an increase in membrane phospholipid flow in recipient cells. These alterations in mechanical properties augment the migration and invasive capabilities of tumor cells, contributing to tumor malignancy. Our findings propose that cellular mechanical properties could serve as new markers for tumor development, and targeting membrane tension may hold potential as a therapeutic strategy.

MERCURY EXPOSURE AND HUMAN REPRODUCTIVE HEALTH (LITERATURE REVIEW)

Mercury (Hg), a highly toxic environmental pollutant, which hazards for human health, including to reproductive system, fertility and pregnancy outcome. Research has shown that Hg could induce impairments in the reproductive function due to cellular deformation of the Leydig cells and the seminiferous tubules, testicular degeneration and degenerative atresia of primordial and primary follicles as well as diminishes the steroidogenesis and synthesis of sex hormones. Some studies investigated miscarriage, spontaneous abortions, stillbirth, and low birth weight due to occupational Hg exposure. This review evaluates the hypothesis that exposure to Hg may. This review evaluates the hypothesis that chronic exposure to mercury can increase the risk of reduced fertility, spontaneous abortion and congenital deficits or abnormalities.

Elasticity of Carrier Fluid: A Key Factor Affecting Mechanical Phenotyping in Deformability Cytometry.

Recently, microfluidics deformability cytometry has emerged as a powerful tool for high-throughput mechanical phenotyping of large populations of cells. These methods characterize cells by their mechanical fingerprints by exerting hydrodynamic forces and monitoring the resulting deformation. These devices have shown great promise for label-free cytometry, yet there is a critical need to improve their accuracy and reconcile any discrepancies with other methods, such as atomic force microscopy. In this study, we employ computational fluid dynamics simulations and uncover how the elasticity of frequently used carrier fluids, such as methylcellulose dissolved in phosphate-buffered saline, is significantly influential to the resulting cellular deformation. We conducted CFD simulations conventionally used within the deformability cytometry field, which neglect fluid elasticity. Subsequently, we incorporated a more comprehensive model that simulates the viscoelastic nature of the carrier fluid. A comparison of the predicted stresses between these two approaches underscores the significance of the emerging elastic stresses in addition to the well-recognized viscous stresses along the channel. Furthermore, we utilize a two-phase flow model to predict the deformation of a promyelocyte (i.e., HL-60 cell type) within a hydrodynamic constriction channel. The obtained results highlight a substantial impact of the elasticity of carrier fluid on cellular deformation and raise questions about the accuracy of mechanical property estimates derived by neglecting elastic stresses.

High throughput cell mechanotyping of cell response to cytoskeletal modulations using a microfluidic cell deformation system.

Cellular mechanical properties influence cellular functions across pathological and physiological systems. The observation of these mechanical properties is limited in part by methods with a low throughput of acquisition or with low accessibility. To overcome these limitations, we have designed, developed, validated, and optimized a microfluidic cellular deformation system (MCDS) capable of mechanotyping suspended cells on a population level at a high throughput rate of ∼300 cells pers second. The MCDS provides researchers with a viable method for efficiently quantifying cellular mechanical properties towards defining prognostic implications of mechanical changes in pathology or screening drugs to modulate cytoskeletal integrity.

The Mechanics of Building Functional Organs.

Organ morphogenesis is multifaceted, multiscale, and fundamentally a robust process. Despite the complex and dynamic nature of embryonic development, organs are built with reproducible size, shape, and function, allowing them to support organismal growth and life. This striking reproducibility of tissue form exists because morphogenesis is not entirely hardwired. Instead, it is an emergent product of mechanochemical information flow, operating across spatial and temporal scales-from local cellular deformations to organ-scale form and function, and back. In this review, we address the mechanical basis of organ morphogenesis, as understood by observations and experiments in living embryos. To this end, we discuss how mechanical information controls the emergence of a highly conserved set of structural motifs that shape organ architectures across the animal kingdom: folds and loops, tubes and lumens, buds, branches, and networks. Moving forward, we advocate for a holistic conceptual framework for the study of organ morphogenesis, which rests on an interdisciplinary toolkit and brings the embryo center stage.

Curved crease origami and topological singularities enable hyperextensibility of L. olor.

Fundamental limits of cellular deformations, such as hyperextension of a living cell, remain poorly understood. Here, we describe how the single-celled protist Lacrymaria olor, a 40-micrometer cell, is capable of reversibly and repeatably extending its necklike protrusion up to 1200 micrometers in 30 seconds. We discovered a layered cortical cytoskeleton and membrane architecture that enables hyperextensions through the folding and unfolding of cellular-scale origami. Physical models of this curved crease origami display topological singularities, including traveling developable cones and cytoskeletal twisted domain walls, which provide geometric control of hyperextension. Our work unravels how cell geometry encodes behavior in single cells and provides inspiration for geometric control in microrobotics and deployable architectures.

Probing the Surface Layer Modulation on Archaeal Mechanics and Adhesion at the Single-Cell Level.

Addressing the challenge of understanding how cellular interfaces dictate the mechanical resilience and adhesion of archaeal cells, this study demonstrates the role of the surface layer (S-layer) in methanogenic archaea. Using a combination of atomic force microscopy and single-cell force spectroscopy, we quantified the impact of S-layer disruption on cell morphology, mechanical properties, and adhesion capabilities. We demonstrate that the S-layer is crucial for maintaining cell morphology, where its removal induces significant cellular enlargement and deformation. Mechanical stability of the cell surface is substantially compromised upon S-layer disruption, as evidenced by decreased Young's modulus values. Adhesion experiments revealed that the S-layer primarily facilitates hydrophobic interactions, which are significantly reduced after its removal, affecting both cell-cell and cell-bubble interactions. Our findings illuminate the S-layer's fundamental role in methanogen architecture and provide a chemical understanding of archaeal cell surfaces, with implications for enhancing methane production in biotechnological applications.

Hydrogen-enhanced densified deformation twins in 304L austenitic stainless steel fabricated by selective laser melting

Twin boundaries are the preferred site for crack nucleation and propagation in a hydrogen-rich environment. The relationship among hydrogen, cellular structure, and deformation twins is significant in further enhancing the resistance to hydrogen embrittlement of austenitic stainless steels produced by SLM. It has been demonstrated that cellular structures with high dislocation densities play a positive role in increasing stress above a critical level for deformation twin formation. The cellular structure affects the distribution of hydrogen, with hydrogen presence at cellular boundaries reducing its accumulation at grain boundaries. Hydrogen increases the density of deformation twins and reduces the thickness of individual deformation twins. This phenomenon can be attributed to an increase in nucleation sites for the deformation twin, which is closely related to the decrease in stacking fault energy and the increase in dislocation density caused by hydrogen. Both cellular structure and deformation twins play a positive role in improving the hydrogen embrittlement resistance of austenitic stainless steels.

A TICT-AIE activated dual-channel fluorescence-on probe to reveal the dynamics mechanosensing of lipid droplets during ferroptosis

Mechanical forces play a crucial role in cellular processes, including ferroptosis, a form of regulated cell death associated with various diseases. However, the mechanical aspects of organelle lipid droplets (LDs) during ferroptosis are poorly understood. In this study, we designed and synthesized a fluorescent probe, TPE-V1, to enable real-time monitoring of LDs' viscosity using a dual-channel fluorescence-on model (red channel at 617 nm and NIR channel at 710 nm). The fluorescent imaging of using TPE-V1 was achieved due to the integrated mechanisms of the twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE). Through dual-emission channel fluorescence imaging, we observed the enhanced mechanical energy of LDs triggering cellular mechanosensing, including ferroptosis and cell deformation. Theoretical calculations confirmed the probe's behavior, showing that high-viscosity media prevented the rotation processes and restored fluorescence quenching in low viscosity. These findings suggest that our TICT-TPE design strategy provides a practical approach to study LDs' mechanical properties during ferroptosis. This development enhances our understanding of the interplay between mechanical forces and LDs, contributing to the knowledge of ferroptotic cell death and potential therapeutic interventions targeting dysregulated cell death processes.

Microfluidic device featuring micro-constrained channels for multi-parametric assessment of cellular biomechanics and high-precision mechanical phenotyping of gastric cells

BackgroundCellular biomechanics plays a significant role in the regulation of cellular physiological and pathological processes. In recent years, multiple methods have been developed to evaluate cellular biomechanics, such as atomic force microscopy (AFM), micropipette aspiration, and magnetic tweezers. However, most of these methods only focus on a single parameter and cannot automate the process at a high-efficiency level. A novel microfluidic method is necessary to achieve the simultaneous multi-parametric measurement of cellular biomechanics and high-precision cellular mechanical phenotyping at high throughput. ResultsTo tackle the issue concerning the low-throughput and cellular single-parameter evaluation, we designed and fabricated a microfluidic chip featuring multiple micro-constrained channels structure, providing a simultaneous multi-parametric assessment of cellular biomechanics, including elastic modulus, recovery capability, and deformability. We compared the biomechanical properties of normal human gastric mucosal epithelial cells (GES-1) and human gastric cancer cells (AGS and MKN-45) by the chip. Results demonstrated that the elastic modulus of GES-1, AGS, and MKN-45 cells decreased sequentially, which was the opposite of their invasiveness and metastasis potential, suggesting the inverse correlation between cellular elastic modulus and malignancy. Meanwhile, the recovery capability and deformability of GES-1, AGS, and MKN-45 cells increased sequentially, demonstrating the positive correlation between cellular deformability and malignancy. Furthermore, multiple parameters were used to distinguish gastric cancer cells from normal gastric cells via machine learning. An accuracy of over 94.8% for identifying gastric cancer cells was achieved. SignificanceThis study provides a deep insight into the biophysical mechanism of gastric cancer metastasis at the single-cell level and possesses great potential to function as a valuable tool for single-cell analysis, thereby facilitating high-precision and high-throughput discrimination of cellular phenotypes that are not easily discernible through single-marker analysis.

In Vitro Cultivation for Glugea plecoglossi (Microsporidia) Isolated from Ayu (Plecoglossus altivelis).

Glugea plecoglossi is an obligate intracellular microsporidium, which poses a significant threat to ayu (Plecoglossus altivelis). In vitro cultivation models are invaluable tools for investigating intracellular microorganisms, including G. plecoglossil. In this study, we attempted to in vitro cultivate G. plecoglossi using primary cultures derived from ayu monocytes/macrophages (MO/MΦ), a murine-derived macrophage cell line RAW264.7, and the epithelioma papulosum cyprini (EPC) cell line. The results demonstrated that MO/MΦ infected with spores exhibited a pronounced immune response which was presented by rapidly high expression levels of inflammatory cytokines, such as PaIL-1β, PaTNF-α, PaIL-10, and PaTGF-β, and detached within 96 h post-infection (hpi). Infected RAW264.7 cells remained capable of stable passage yet exhibited cellular deformation with a decrease in intracellular spores occurring around 8 days post-infection (dpi). In contrast, EPC cells promised a substantial parasite population, and the cytokine expression levels returned to normal by 8 dpi. In addition, G. plecoglossi spores recovered from EPC cells could infect young ayu, suggesting that EPC cells might be used as an in vitro cultivation system for G. plecoglossi.

Siderophore of plant growth promoting rhizobacterium origin reduces reactive oxygen species mediated injury in Solanum spp. caused by fungal pathogens.

The study aims to explore antifungal properties of bacillibactin siderophore produced by the plant growth-promoting rhizobacterium (PGPR) Bacillus subtilis against fungal phytopathogens Alternaria porri and Fusarium equiseti isolated from Solanum lycopersicum and Solanum melongena plants. Alternaria porri and F. equiseti were isolated from infected plants of eggplant and tomato, respectively. A plate assay was employed to assess the effect of bacillibactin against the phytopathogens. The antifungal potential of the PGPR was evaluated by estimation of dry fungal biomass, visualization of cellular deformity using compound and scanning electron microscopy, antioxidative enzyme assay and analysis of membrane damage via using lipid peroxidation. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis was employed to investigate changes in intracellular iron content. The impact of bacillibactin on pathogenesis was evaluated by infecting detached leaves of S. lycopersicum and S. melongena plants with both the pathogens and treating the infected leaves with bacillibactin. Leaves were further investigated for ROS accumulation, extent of necrosis and cell death. Our findings revealed significant damage to the hyphal structure of A. porri and F. equiseti following treatment with bacillibactin. Biomass reduction, elevated antioxidative enzyme levels, and membrane damage further substantiated the inhibitory effects of the siderophore on fungal growth. ICP-AES analysis indicates an increase in intracellular iron content suggesting enhanced iron uptake facilitated by bacillibactin. Moreover, application of 1500µg ml-1 bacillibactin on infected leaves demonstrated a substantial inhibition of ROS accumulation, necrosis, and cell death upon bacillibactin treatment. This study confirms the potent antagonistic activity of bacillibactin against both the phytopathogens A. porri and F. equiseti growth, supporting its potential as a promising biological control agent for fungal plant diseases. Bacillibactin-induced morphological, physiological, and biochemical alterations in the isolated fungi and pathogen-infected leaves highlight the prospects of bacillibactin as an effective and sustainable solution to mitigate economic losses associated with fungal infections in vegetable crops.

OMEF biochip for evaluating red blood cell deformability using dielectrophoresis as a diagnostic tool for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a prevalent and debilitating disease with numerous health risks, including cardiovascular diseases, kidney dysfunction, and nerve damage. One important aspect of T2DM is its association with the abnormal morphology of red blood cells (RBCs), which leads to increased blood viscosity and impaired blood flow. Therefore, evaluating the mechanical properties of RBCs is crucial for understanding the role of T2DM in cellular deformability. This provides valuable insights into disease progression and potential diagnostic applications. In this study, we developed an open micro-electro-fluidic (OMEF) biochip technology based on dielectrophoresis (DEP) to assess the deformability of RBCs in T2DM. The biochip facilitates high-throughput single-cell RBC stretching experiments, enabling quantitative measurements of the cell size, strain, stretch factor, and post-stretching relaxation time. Our results confirm the significant impact of T2DM on the deformability of RBCs. Compared to their healthy counterparts, diabetic RBCs exhibit ∼27% increased size and ∼29% reduced stretch factor, suggesting potential biomarkers for monitoring T2DM. The observed dynamic behaviors emphasize the contrast between the mechanical characteristics, where healthy RBCs demonstrate notable elasticity and diabetic RBCs exhibit plastic behavior. These differences highlight the significance of mechanical characteristics in understanding the implications for RBCs in T2DM. With its ∼90% sensitivity and rapid readout (ultimately within a few minutes), the OMEF biochip holds potential as an effective point-of-care diagnostic tool for evaluating the deformability of RBCs in individuals with T2DM and tracking disease progression.

Cellular elasticity in cancer: a review of altered biomechanical features.

A large number of studies have shown that changes in biomechanical characteristics are an important indicator of tumor transformation in normal cells. Elastic deformation is one of the more studied biomechanical features of tumor cells, which plays an important role in tumourigenesis and development. Altered cell elasticity often brings many indications. This manuscript reviews the effects of altered cellular elasticity on cell characteristics, including adhesion viscosity, migration, proliferation, and differentiation elasticity and stiffness. Also, the physical factors that may affect cell elasticity, such as temperature, cell height, cell-viscosity, and aging, are summarized. Then, the effects of cell-matrix, cytoskeleton, in vitro culture medium, and cell-substrate with different three-dimensional structures on cell elasticity during cell tumorigenesis are outlined. Importantly, we summarize the current signaling pathways that may affect cellular elasticity, as well as tests for cellular elastic deformation. Finally, we summarize current hybrid materials: polymer-polymer, protein-protein, and protein-polymer hybrids, also, nano-delivery strategies that target cellular resilience and cases that are at least in clinical phase 1 trials. Overall, the behavior of cancer cell elasticity is modulated by biological, chemical, and physical changes, which in turn have the potential to alter cellular elasticity, and this may be an encouraging prediction for the future discovery of cancer therapies.

Investigation of nanoparticles on cell elasticity using the nanoindentation method

Nowadays, the biomechanics of living cells has been the focus of attention, as high-resolution techniques such as atomic force microscopy (AFM) allow the properties of living cells to be studied with nanoscale and precision. There are a lot of results showing that the mechanical changes in the cell or its extracellular matrix (ECM) are used as a biomarker of pathological changes. Therefore, cell stiffness is an index that evaluates the status of cell cultures. Elastic properties of cells can be deduced by nanoindentation experiments with AFM. The quantitative parameter that determines cellular deformation in the nanoindentation experiment is Young’s modulus. In recent studies, it has also been shown that gold nanostructures (Au-NP) can play an active role in the detection-diagnosis of diseases and/or targeting tumor and inflammatory cells for therapeutic reasons. In this study, first of all, 2D axial biomechanical models of keratinocytes and glioma cells were made with the Finite Element Method (FEM modeling) and their mechanical properties were calculated. The deformation and mechanical changes that occur in the cell during the uptake and distribution of gold nanostructures were also investigated through the modeling. Keratinocyte cells modeled in the study are epidermal cells that make keratin, and Glioma is a group of tumor cells formed in glial cell cells, which are the supporting tissue of the brain. The Young Modulus values ​​calculated using the Hertz model and elasticity values obtained from different techniques in the literature were compared with the simulation outputs.

Ligand Binding-Induced Cellular Membrane Deformation is Correlated with the Changes in Membrane Stiffness.

Study interaction between ligands and protein receptors is a key step for biomarker research and drug discovery. In situ measurement of cell surface membrane protein binding on whole cells eliminates the cost and pitfalls associated with membrane protein purification. Ligand binding to membrane protein was recently found to induce nanometer-scale cell membrane deformations, which can be monitored with real-time optical imaging to quantify ligand/protein binding kinetics. However, the insight into this phenomenon has still not been fully understood. We hypothesize that ligand binding can change membrane stiffness, which induces membrane deformation. To investigate this, cell height and membrane stiffness changes upon ligand binding are measured using atomic force microscopy (AFM). Wheat germ agglutinin (WGA) is used as a model ligand that binds to the cell surface glycoprotein. The changes in cell membrane stiffness and cell height upon ligand bindings are determined for three different cell lines (human A431, HeLa, and rat RBL-2H3) on two different substrates. AFM results show that cells become stiffer with increased height after WGA modification for all cases studied. The increase in cell membrane stiffness is further confirmed by plasmonic scattering microscopy, which shows an increased cell spring constant upon WGA binding. Therefore, this study provides direct experimental evidence that the membrane stiffness changes are directly correlated with ligand binding-induced cell membrane deformation.