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Confluent monolayers of human umbilical vein endothelial cells (HUVECs) on a poly(2-methoxyethyl acrylate) (PMEA) antithrombogenic surface play a major role in mimicking the inner surface of native blood vessels. In this study, we extensively investigated the behavior of cell–polymer and cell–cell interactions by measuring adhesion strength using single-cell force spectroscopy. In addition, the attachment and migration of HUVECs on PMEA-analogous substrates were detected, and the migration rate was estimated. Moreover, the bilateral migration of HUVECs between two adjacent surfaces was observed. Furthermore, the outer surface of HUVEC was examined using frequency-modulation atomic force microscopy (FM-AFM). Hydration was found to be an indication of a healthy glycocalyx layer. The results were compared with the hydration states of individual PMEA-analogous polymers to understand the adhesion mechanism between the cells and substrates in the interface region. HUVECs could attach and spread on the PMEA surface with stronger adhesion strength than self-adhesion strength, and migration occurred over the surface of analogue polymers. We confirmed that platelets could not adhere to HUVEC monolayers cultured on the PMEA surface. FM-AFM images revealed a hydration layer on the HUVEC surfaces, indicating the presence of components of the glycocalyx layer in the presence of intermediate water. Our findings show that PMEA can mimic original blood vessels through an antithrombogenic HUVEC monolayer and is thus suitable for the construction of artificial small-diameter blood vessels.

The architecture of focal adhesions The physical linkage between the extracellular matrix and the actin cytoskeleton of a cell is made by structures known as focal adhesions, acting through integrin receptors. They are of fundamental importance in human physiology because they mediate cell adhesion, mechanosensing and signalling for the control of cell growth and differentiation. The molecular architecture of focal adhesions has now been determined using three-dimensional super-resolution fluorescence microscopy to map protein organization at the nanoscale level. They are revealed as well-organized ultrastructures in which integrins and actin are separated by a 40-nanometre-long core consisting of partially overlapping protein-specific layers, spanned by talin tethers. The multilaminar architecture creates three or more separate compartments that mediate the interdependent functions of focal adhesions. Focal adhesions link the extracellular matrix by integrin receptors to cytoplasmic actin filaments and are fundamental to human physiology. These authors determine the molecular architecture of focal adhesions by mapping protein organization at the nanoscale level. The results demonstrate that focal adhesions possess a well-organized ultrastructure made up of at least three spatial and functional compartments that mediate their interdependent functions. Cell adhesions to the extracellular matrix (ECM) are necessary for morphogenesis, immunity and wound healing 1 , 2 . Focal adhesions are multifunctional organelles that mediate cell–ECM adhesion, force transmission, cytoskeletal regulation and signalling 1 , 2 , 3 . Focal adhesions consist of a complex network 4 of trans-plasma-membrane integrins and cytoplasmic proteins that form a <200-nm plaque 5 , 6 linking the ECM to the actin cytoskeleton. The complexity of focal adhesion composition and dynamics implicate an intricate molecular machine 7 , 8 . However, focal adhesion molecular architecture remains unknown. Here we used three-dimensional super-resolution fluorescence microscopy (interferometric photoactivated localization microscopy) 9 to map nanoscale protein organization in focal adhesions. Our results reveal that integrins and actin are vertically separated by a ∼40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signalling layer containing integrin cytoplasmic tails, focal adhesion kinase and paxillin; an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin, vasodilator-stimulated phosphoprotein and α-actinin. By localizing amino- and carboxy-terminally tagged talins, we reveal talin’s polarized orientation, indicative of a role in organizing the focal adhesion strata. The composite multilaminar protein architecture provides a molecular blueprint for understanding focal adhesion functions.

This comprehensive work discusses novel biomolecular surfaces that have been engineered to either control or measure cell function at the atomic, molecular, and cellular levels. Each chapter presents real results, concepts, and expert perspectives of how cells interact with biomolecular surfaces, with particular emphasis on interactions within complex mechanical environments such as in the cardiovascular system. In addition, the book provides detailed coverage of inflammation and cellular immune response as a useful model for how engineering concepts and tools may be effectively applied to complex systems in biomedicine. -Accessible to biologists looking for new ways to model their results and engineers interested in biomedical applications -Useful to researchers in biomaterials, inflammation, and vascular biology -Excellent resource for graduate students as a textbook in cell tissue engineering or cell mechanics courses

Integrins mediate cell adhesion to the extracellular matrix and transmit signals within the cell that stimulate cell spreading, retraction, migration, and proliferation. The mechanism of integrin outside-in signaling has been unclear. We found that the heterotrimeric guanine nucleotide-binding protein (G protein) Gα₁₃ directly bound to the integrin β₃ cytoplasmic domain and that Gα₁₃-integrin interaction was promoted by ligand binding to the integrin αIIbβ₃ and by guanosine triphosphate (GTP) loading of Gα₁₃. Interference of Gα₁₃ expression or a myristoylated fragment of Gα₁₃ that inhibited interaction of αIIbβ₃ with Gα₁₃ diminished activation of protein kinase c-Src and stimulated the small guanosine triphosphatase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are noncanonical Gα₁₃-coupled receptors that provide a mechanism for dynamic regulation of RhoA.

Epithelial tissues maintain a robust architecture which is important for their barrier function, but they are also remodelled through the reorganization of cell–cell contacts. Tissue stability requires intercellular adhesion mediated by E-cadherin, in particular its trans-association in homophilic complexes supported by actin filaments through β- and α-catenin. How α-catenin dynamic interactions between E-cadherin/β-catenin and cortical actin control both stability and remodelling of adhesion is unclear. Here we focus on Drosophila homophilic E-cadherin complexes rather than total E-cadherin, including diffusing ‘free’ E-cadherin, because these complexes are a better proxy for adhesion. We find that E-cadherin complexes partition in very stable microdomains (that is, bona fide adhesive foci which are more stable than remodelling contacts). Furthermore, we find that stability and mobility of these microdomains depend on two actin populations: small, stable actin patches concentrate at homophilic E-cadherin clusters, whereas a rapidly turning over, contractile network constrains their lateral movement by a tethering mechanism. α-Catenin controls epithelial architecture mainly through regulation of the mobility of homophilic clusters and it is largely dispensable for their stability. Uncoupling stability and mobility of E-cadherin complexes suggests that stable epithelia may remodel through the regulated mobility of very stable adhesive foci. E-cadherin: Two-tier stabilization and immobilization mechanism Adhesion mediated by E-cadherin requires its trans-association in homophilic complexes stabilized by actin filaments. In this study Cavey et al . show that homophilic complexes partition in very stable microdomains. Stability and lateral mobility of these microdomains depends on two distinct actin populations: small, stable actin patches stabilize homophilic E-cadherin clusters, whereas a rapidly turning over, contractile network constrains lateral diffusion by a tethering mechanism. Alpha-catenin controls epithelial architecture mainly via the regulation of homophilic clusters mobility and is largely dispensable for their stability. A study showing that homophilic E-cadherin complexes partition in very stable microdomains. Stability and lateral mobility of these microdomains depend on two distinct actin populations: small, stable actin patches stabilize homophilic E-cadherin clusters, whereas a rapidly turning over, contractile network constrains lateral diffusion by a tethering mechanism.

Cell-to-cell communication is a crucial prerequisite for the development and maintenance of multicellular organisms. To date, diverse mechanisms of intercellular exchange of information have been documented, including chemical synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive nanotubular structures formed de novo between cells that create complex networks. These structures facilitate the selective transfer of membrane vesicles and organelles but seem to impede the flow of small molecules. Accordingly, we propose a novel biological principle of cell-to-cell interaction based on membrane continuity and intercellular transfer of organelles.

Almost every vertebrate cell has a specialized cell surface projection called a primary cilium. Although these structures were first described more than a century ago, the full scope of their functions remains poorly understood. Here, we review emerging evidence that in addition to their well-established roles in sight, smell, and mechanosensation, primary cilia are key participants in intercellular signaling. This new appreciation of primary cilia as cellular antennae that sense a wide variety of signals could help explain why ciliary defects underlie such a wide range of human disorders, including retinal degeneration, polycystic kidney disease, Bardet-Biedl syndrome, and neural tube defects.

Competitive interactions between cells are the basis of many homeostatic processes in biology. Some of the best-described cases of competition between cells occur in DROSOPHILA: cell competition, whereby somatic cells within a growing epithelium compete with one another for contribution to the adult, and stem cell competition, in which germline or somatic stem cells vie for residency in the niche. Both types of competition are conserved physiological processes, with much to tell us about how cellular neighborhoods influence cell behavior, and have importance to stem cell biology, regeneration and transplantation, and cancer.

Monocytes contribute to the development of atherosclerotic lesions in mouse models 1 , 3 . The chemoattractant proteins (chemokines), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human atheroma 4 , 5 , and mice lacking receptors for these chemokines are less susceptible to atherosclerosis and have fewer monocytes in vascular lesions 6 , 7 . Although MCP-1 has a powerful effect on monocytes, IL-8 is thought to act predominantly on neutrophils and it is unclear howit could recruit monocytes 6 , 8 . Here we investigate the ability of chemokines to control the interaction of monocytes under flow conditions with vascular endothelium that has been transduced to express specific leukocyte-adherence receptors. We find that MCP-1 and IL-8 can each rapidly cause rolling monocytes to adhere firmly onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium transient or chemotaxis. We conclude that chemokines are important modulators of monocyte–endothelial interactions under flow conditions. Moreover, our finding that IL-8 is a powerful trigger for firm adhesion of monocytes to vascular endothelium reveals an unexpected role for this chemokine in monocyte recruitment.

Cadherins are transmembrane proteins that mediate adhesion between cells in the solid tissues of animals. Here we present the 3.1 angstrom resolution crystal structure of the whole, functional extracellular domain from C-cadherin, a representative \"classical\" cadherin. The structure suggests a molecular mechanism for adhesion between cells by classical cadherins, and it provides a new framework for understanding both cis (same cell) and trans (juxtaposed cell) cadherin interactions. The trans adhesive interface is a twofold symmetric interaction defined by a conserved tryptophan side chain at the membrane-distal end of a cadherin molecule from one cell, which inserts into a hydrophobic pocket at the membrane-distal end of a cadherin molecule from the opposing cell.