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1

Biswas, Kabir H., and Jay T. Groves. "Hybrid Live Cell–Supported Membrane Interfaces for Signaling Studies." Annual Review of Biophysics 48, no. 1 (2019): 537–62. http://dx.doi.org/10.1146/annurev-biophys-070317-033330.

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A wide range of cell–microenvironmental interactions are mediated by membrane-localized receptors that bind ligands present on another cell or the extracellular matrix. This situation introduces a number of physical effects including spatial organization of receptor–ligand complexes and development of mechanical forces in cells. Unlike traditional experimental approaches, hybrid live cell–supported lipid bilayer (SLB) systems, wherein a live cell interacts with a synthetic substrate supported membrane, allow interrogation of these aspects of receptor signaling. The SLB system directly offers f
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2

Daniel, Susan, Fernando Albertorio, and Paul S. Cremer. "Making Lipid Membranes Rough, Tough, and Ready to Hit the Road." MRS Bulletin 31, no. 7 (2006): 536–40. http://dx.doi.org/10.1557/mrs2006.139.

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Solid-supported lipid bilayers hold strong promise as bioanalytical sensor platforms because they readily mimic the same multivalent ligand-receptor interactions that occur in real cells. Such devices might be used to monitor air and water quality under real-world conditions. At present, however, supported membranes are considered too fragile to survive the harsh environments typically required for non-laboratory use. Specifically, they lack the resiliency to withstand air exposure and the thermal and mechanical stresses associated with device transport, storage, and continuous use over long p
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3

Di Iorio, Daniele, Yao Lu, Joris Meulman, and Jurriaan Huskens. "Recruitment of receptors at supported lipid bilayers promoted by the multivalent binding of ligand-modified unilamellar vesicles." Chemical Science 11, no. 12 (2020): 3307–15. http://dx.doi.org/10.1039/d0sc00518e.

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The development of model systems that mimic biological interactions and allow the control of both receptor and ligand densities, is essential for a molecular understanding of biomolecular processes, such as the recruitment of receptors at interfaces.
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4

Alves, Anna Carolina Schneider, Reinaldo Antonio Dias, Luciano Porto Kagami, et al. "Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells." Current Medicinal Chemistry 25, no. 18 (2018): 2082–104. http://dx.doi.org/10.2174/0929867325666180111100601.

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For more than 40 years, the fluid mosaic model of cellular membranes has supported our vision of an inert lipid bilayer containing membrane protein receptors that are randomly hit by extracellular molecules to trigger intracellular signaling events. However, the notion that compartmentalized cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts) spatially arrange receptors and effectors to promote kinetically favorable interactions necessary for the signal transduction sounds much more realistic. Despite their assumed importance for the dynamics of ligand-receptor int
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5

Ghosh Moulick, R., D. Afanasenkau, S. E. Choi, et al. "Reconstitution of Fusion Proteins in Supported Lipid Bilayers for the Study of Cell Surface Receptor–Ligand Interactions in Cell–Cell Contact." Langmuir 32, no. 14 (2016): 3462–69. http://dx.doi.org/10.1021/acs.langmuir.5b04644.

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6

Jönsson, Peter, Jennifer H. Southcombe, Ana Mafalda Santos, et al. "Remarkably low affinity of CD4/peptide-major histocompatibility complex class II protein interactions." Proceedings of the National Academy of Sciences 113, no. 20 (2016): 5682–87. http://dx.doi.org/10.1073/pnas.1513918113.

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The αβ T-cell coreceptor CD4 enhances immune responses more than 1 million-fold in some assays, and yet the affinity of CD4 for its ligand, peptide-major histocompatibility class II (pMHC II) on antigen-presenting cells, is so weak that it was previously unquantifiable. Here, we report that a soluble form of CD4 failed to bind detectably to pMHC II in surface plasmon resonance-based assays, establishing a new upper limit for the solution affinity at 2.5 mM. However, when presented multivalently on magnetic beads, soluble CD4 bound pMHC II-expressing B cells, confirming that it is active and al
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7

Zhang, Yun, Yongzhi Qiu, Aaron T. Blanchard, et al. "Platelet integrins exhibit anisotropic mechanosensing and harness piconewton forces to mediate platelet aggregation." Proceedings of the National Academy of Sciences 115, no. 2 (2017): 325–30. http://dx.doi.org/10.1073/pnas.1710828115.

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Platelet aggregation at the site of vascular injury is essential in clotting. During this process, platelets are bridged by soluble fibrinogen that binds surface integrin receptors. One mystery in the mechanism of platelet aggregation pertains to how resting platelets ignore soluble fibrinogen, the third most abundant protein in the bloodstream, and yet avidly bind immobile fibrinogen on the surface of other platelets at the primary injury site. We speculate that platelet integrins are mechanosensors that test their ligands across the platelet–platelet synapse. To investigate this model, we in
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8

Wang, Li, Xin-Pu Hou, Angelica Ottova, and H. Ti Tien. "Receptor–ligand interactions in a reconstituted bilayer lipid membrane." Electrochemistry Communications 2, no. 5 (2000): 287–89. http://dx.doi.org/10.1016/s1388-2481(00)00008-4.

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9

Zhdanov, Vladimir P. "Ligand-receptor-mediated attachment of lipid vesicles to a supported lipid bilayer." European Biophysics Journal 49, no. 5 (2020): 395–400. http://dx.doi.org/10.1007/s00249-020-01441-0.

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10

Torres, Manuel, Catalina Ana Rosselló, Paula Fernández-García, Victoria Lladó, Or Kakhlon, and Pablo Vicente Escribá. "The Implications for Cells of the Lipid Switches Driven by Protein–Membrane Interactions and the Development of Membrane Lipid Therapy." International Journal of Molecular Sciences 21, no. 7 (2020): 2322. http://dx.doi.org/10.3390/ijms21072322.

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The cell membrane contains a variety of receptors that interact with signaling molecules. However, agonist–receptor interactions not always activate a signaling cascade. Amphitropic membrane proteins are required for signal propagation upon ligand-induced receptor activation. These proteins localize to the plasma membrane or internal compartments; however, they are only activated by ligand-receptor complexes when both come into physical contact in membranes. These interactions enable signal propagation. Thus, signals may not propagate into the cell if peripheral proteins do not co-localize wit
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11

Nair, Pradeep M., Heather Flores, Alvin Gogineni, et al. "Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display." Proceedings of the National Academy of Sciences 112, no. 18 (2015): 5679–84. http://dx.doi.org/10.1073/pnas.1418962112.

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TNF superfamily death ligands are expressed on the surface of immune cells and can trigger apoptosis in susceptible cancer cells by engaging cognate death receptors. A recombinant soluble protein comprising the ectodomain of Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has shown remarkable preclinical anticancer activity but lacked broad efficacy in patients, possibly owing to insufficient exposure or potency. We observed that antibody cross-linking substantially enhanced cytotoxicity of soluble Apo2L/TRAIL against diverse cancer cell lines. Presentation of the ligand on gla
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12

Higo, Junichi, Kota Kasahara, Mitsuhito Wada, et al. "Free-energy landscape of molecular interactions between endothelin 1 and human endothelin type B receptor: fly-casting mechanism." Protein Engineering, Design and Selection 32, no. 7 (2019): 297–308. http://dx.doi.org/10.1093/protein/gzz029.

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Abstract The free-energy landscape of interaction between a medium-sized peptide, endothelin 1 (ET1), and its receptor, human endothelin type B receptor (hETB), was computed using multidimensional virtual-system coupled molecular dynamics, which controls the system’s motions by introducing multiple reaction coordinates. The hETB embedded in lipid bilayer was immersed in explicit solvent. All molecules were expressed as all-atom models. The resultant free-energy landscape had five ranges with decreasing ET1–hETB distance: completely dissociative, outside-gate, gate, binding pocket, and genuine-
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13

Menon, Santosh T., May Han, and Thomas P. Sakmar. "Rhodopsin: Structural Basis of Molecular Physiology." Physiological Reviews 81, no. 4 (2001): 1659–88. http://dx.doi.org/10.1152/physrev.2001.81.4.1659.

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The crystal structure of rod cell visual pigment rhodopsin was recently solved at 2.8-Å resolution. A critical evaluation of a decade of structure-function studies is now possible. It is also possible to begin to explain the structural basis for several unique physiological properties of the vertebrate visual system, including extremely low dark noise levels as well as high gain and color detection. The ligand-binding pocket of rhodopsin is remarkably compact, and several apparent chromophore-protein interactions were not predicted from extensive mutagenesis or spectroscopic studies. The trans
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14

Wakefield, Devin L., David Holowka та Barbara Baird. "The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces". Molecular Biology of the Cell 28, № 23 (2017): 3383–96. http://dx.doi.org/10.1091/mbc.e17-03-0208.

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We examined the spatial targeting of early and downstream signaling mediated by the immunoglobulin E (IgE) receptor (FcεRI) in RBL mast cells using surface-patterned 2,4-dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge concentrated for DNP-BSA. These distributions of IgE-FcεRI propa
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15

Chen, Zhongwen, Dongmyung Oh, Kabir H. Biswas, Cheng-Han Yu, Ronen Zaidel-Bar, and Jay T. Groves. "Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility." Proceedings of the National Academy of Sciences 115, no. 25 (2018): E5696—E5705. http://dx.doi.org/10.1073/pnas.1719961115.

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Recent studies have revealed pronounced effects of the spatial distribution of EphA2 receptors on cellular response to receptor activation. However, little is known about molecular mechanisms underlying this spatial sensitivity, in part due to lack of experimental systems. Here, we introduce a hybrid live-cell patterned supported lipid bilayer experimental platform in which the sites of EphA2 activation and integrin adhesion are spatially controlled. Using a series of live-cell imaging and single-molecule tracking experiments, we map the transmission of signals from ephrinA1:EphA2 complexes. R
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16

Loy, Dominik M., Philipp M. Klein, Rafał Krzysztoń, Ulrich Lächelt, Joachim O. Rädler, and Ernst Wagner. "A microfluidic approach for sequential assembly of siRNA polyplexes with a defined structure-activity relationship." PeerJ Materials Science 1 (October 15, 2019): e1. http://dx.doi.org/10.7717/peerj-matsci.1.

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Therapeutic nucleic acids provide versatile treatment options for hereditary or acquired diseases. Ionic complexes with basic polymers are frequently used to facilitate nucleic acid’s transport to intracellular target sites. Usually, these polyplexes are prepared manually by mixing two components: polyanionic nucleic acids and polycations. However, parameters such as internal structure, size, polydispersity and surface charge of the complexes sensitively affect pharmaceutical efficiency. Hence a controlled assembly is of paramount importance in order to ensure high product quality. In the curr
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17

Jahn, Thomas, Stacie Gooch, Jaqueline Rogerio, and Kenneth Weinberg. "Spatiotemporal Regulation of C-Kit Signaling through Lipid Rafts." Blood 104, no. 11 (2004): 819. http://dx.doi.org/10.1182/blood.v104.11.819.819.

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Abstract Recently, the understanding of membrane receptors has been transformed by studies characterizing the topology of the plasma membrane. The T-cell receptor (TCR) has been most studied for interactions of receptors with the lipid bilayer. TCR signaling has been shown to be dependent on the localization of the TCR complex to specific cholesterol- and sphingolipid-rich membrane subdomains, also called microdomains or lipid rafts. The definition of lipid rafts as assembly platforms to initiate membrane receptor signaling has induced a novel view of the plasma membrane as a compartmentalized
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18

van Belkum, Alex, Carina Almeida, Benjamin Bardiaux, et al. "Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens." Diagnostics 11, no. 7 (2021): 1259. http://dx.doi.org/10.3390/diagnostics11071259.

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Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in
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19

Li, Long, Bernd Stumpf, and Ana-Sunčana Smith. "Molecular Biomechanics Controls Protein Mixing and Segregation in Adherent Membranes." International Journal of Molecular Sciences 22, no. 7 (2021): 3699. http://dx.doi.org/10.3390/ijms22073699.

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Cells interact with their environment by forming complex structures involving a multitude of proteins within assemblies in the plasma membrane. Despite the omnipresence of these assemblies, a number of questions about the correlations between the organisation of domains and the biomechanical properties of the involved proteins, namely their length, flexibility and affinity, as well as about the coupling to the elastic, fluctuating membrane, remain open. Here we address these issues by developing an effective Kinetic Monte Carlo simulation to model membrane adhesion. We apply this model to a ty
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20

Wilmes, Stephan, Maximillian Hafer, Tess A. Stanly, et al. "New Paradigms for the Mechanisms of Thrombopoietin Receptor Activation and Dysregulation By the JAK2V617F Mutation." Blood 134, Supplement_1 (2019): 2962. http://dx.doi.org/10.1182/blood-2019-129234.

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Janus kinase (JAK2)V617F is the most common mutation found in patients with Philadelphia chromosome negative myeloproliferative neoplasms (Ph- MPNs). The discovery of this mutation over 15 years ago revolutionised MPN diagnosis and inspired the development of JAK inhibitors as new therapeutic interventions. However, despite extensive structural and biophysical studies using JAK2 domains in isolation, the exact molecular mechanisms of JAK2V617F activation remains elusive. We have previously demonstrated that expression of the thrombopoietin (TPO) receptor, MPL, which interacts directly with JAK
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21

Salo-Ahen, Outi M. H., Ida Alanko, Rajendra Bhadane, et al. "Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development." Processes 9, no. 1 (2020): 71. http://dx.doi.org/10.3390/pr9010071.

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Molecular dynamics (MD) simulations have become increasingly useful in the modern drug development process. In this review, we give a broad overview of the current application possibilities of MD in drug discovery and pharmaceutical development. Starting from the target validation step of the drug development process, we give several examples of how MD studies can give important insights into the dynamics and function of identified drug targets such as sirtuins, RAS proteins, or intrinsically disordered proteins. The role of MD in antibody design is also reviewed. In the lead discovery and lea
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22

Saha, Asim, Roddy S. O'Connor, Govindarajan Thangavelu, et al. "Loss of Programmed Death Ligand-1 Expression on Donor T Cells Lessens Acute Graft-Versus-Host Disease Lethality." Blood 126, no. 23 (2015): 147. http://dx.doi.org/10.1182/blood.v126.23.147.147.

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Abstract The PD-1/PD-L1 pathway plays an important role in regulation of alloimmune responses and in induction and maintenance of peripheral tolerance. Because GVHD is driven by donor T cells and PD-L1 expression can be markedly elevated on T cells during activation, we investigated the functional significance of PD-L1 expressed by donor T cells in regulating murine models of acute GVHD. PD-L1 expression was up-regulated on donor CD4 and CD8 T cells during GVHD. We considered the possibility that PD-L1 expression on activated donor T cells might inhibit GVHD by down regulating donor anti-host
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23

Li, Xuerong, Huiqing Chen, Steven S. Oh, and Athar H. Chishti. "A Novel Plasmodium falciparum Microneme Protein Interacts with Host Band 3 during Red Cell Invasion." Blood 108, no. 11 (2006): 539. http://dx.doi.org/10.1182/blood.v108.11.539.539.

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Abstract Clinical manifestation of Plasmodium falciparum malaria is directly linked to the blood stage of the parasite life cycle. At the blood stage, circulating merozoites invade red blood cells (RBCs) through multiple receptor-ligand interactions that mediate a complex series of events in a period of approximately one minute. Certain strains of P. falciparum favor an invasion mechanism that depends on sialic acid residues on the host RBC surface, while other strains favor a sialic acid-independent mechanism to invade RBCs. Two putative non-glycosylated extracellular regions of human RBC ban
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24

Lee, Donggeun, Woo Hyuk Jung, Suho Lee, et al. "Ionic contrast across a lipid membrane for Debye length extension: towards an ultimate bioelectronic transducer." Nature Communications 12, no. 1 (2021). http://dx.doi.org/10.1038/s41467-021-24122-8.

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AbstractDespite technological advances in biomolecule detections, evaluation of molecular interactions via potentiometric devices under ion-enriched solutions has remained a long-standing problem. To avoid severe performance degradation of bioelectronics by ionic screening effects, we cover probe surfaces of field effect transistors with a single film of the supported lipid bilayer, and realize respectable potentiometric signals from receptor–ligand bindings irrespective of ionic strength of bulky solutions by placing an ion-free water layer underneath the supported lipid bilayer. High-energy
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25

Dam, Tommy, Victoria Junghans, Jane Humphrey, Manto Chouliara, and Peter Jönsson. "Calcium Signaling in T Cells Is Induced by Binding to Nickel-Chelating Lipids in Supported Lipid Bilayers." Frontiers in Physiology 11 (January 21, 2021). http://dx.doi.org/10.3389/fphys.2020.613367.

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Supported lipid bilayers (SLBs) are one of the most common cell-membrane model systems to study cell-cell interactions. Nickel-chelating lipids are frequently used to functionalize the SLB with polyhistidine-tagged ligands. We show here that these lipids by themselves can induce calcium signaling in T cells, also when having protein ligands on the SLB. This is important to avoid “false” signaling events in cell studies with SLBs, but also to better understand the molecular mechanisms involved in T-cell signaling. Jurkat T cells transfected with the non-signaling molecule rat CD48 were found to
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26

Felce, James H., Lucia Parolini, Erdinc Sezgin, et al. "Single-Molecule, Super-Resolution, and Functional Analysis of G Protein-Coupled Receptor Behavior Within the T Cell Immunological Synapse." Frontiers in Cell and Developmental Biology 8 (January 18, 2021). http://dx.doi.org/10.3389/fcell.2020.608484.

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A central process in immunity is the activation of T cells through interaction of T cell receptors (TCRs) with agonistic peptide-major histocompatibility complexes (pMHC) on the surface of antigen presenting cells (APCs). TCR-pMHC binding triggers the formation of an extensive contact between the two cells termed the immunological synapse, which acts as a platform for integration of multiple signals determining cellular outcomes, including those from multiple co-stimulatory/inhibitory receptors. Contributors to this include a number of chemokine receptors, notably CXC-chemokine receptor 4 (CXC
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27

Ottova, A. Leitmannova, and H. Ti Tien. "Ligand-Receptor Contact Interactions Using Self-Assembled Bilayer Lipid Membranes." MRS Proceedings 360 (1994). http://dx.doi.org/10.1557/proc-360-339.

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AbstractBiological membranes play a crucial role in signal transduction and information processing as well as in energy conversion. This is owing to the fact that most physiological activities involve some kind of lipid bilayer-based receptor-ligand contact interactions. There are many outstanding examples such as ion sensing, antigen-antibody binding, and ligand/voltage--gated channels, to name a few. One approach to study these interactions in vitro is facilitated by employing artificial bilayer lipid membranes (BLMs). We have focused the efforts on ion and/or molecular selectivity and speci
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28

Li, Long, Jinglei Hu, Huaping Wu, and Fan Song. "Cis-interaction of ligands on a supported lipid bilayer affects their binding to cell adhesion receptors." Science China Physics, Mechanics & Astronomy 64, no. 10 (2021). http://dx.doi.org/10.1007/s11433-021-1752-0.

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29

Li, Long, Xiaohuan Wang, Helong Wu, Yingfeng Shao, Huaping Wu, and Fan Song. "Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion." Frontiers in Molecular Biosciences 8 (April 12, 2021). http://dx.doi.org/10.3389/fmolb.2021.655662.

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Cell-cell adhesion and the adhesion of cells to extracellular matrix are mediated by the specific binding of receptors on the cell membrane to their cognate ligands on the opposing surface. The adhesion receptors can exhibit affinity for nanoscale lipid clusters that form in the cell membrane. Experimental studies of such adhesion systems often involve a cell adhering either to a solid surface with immobile ligands or a supported lipid bilayer with mobile ligands. A central question in these cell-substrate adhesions is how the mobility of the ligands physically affects their binding to the adh
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30

Banjade, Sudeep, and Michael K. Rosen. "Phase transitions of multivalent proteins can promote clustering of membrane receptors." eLife 3 (October 16, 2014). http://dx.doi.org/10.7554/elife.04123.

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Clustering of proteins into micrometer-sized structures at membranes is observed in many signaling pathways. Most models of clustering are specific to particular systems, and relationships between physical properties of the clusters and their molecular components are not well understood. We report biochemical reconstitution on supported lipid bilayers of protein clusters containing the adhesion receptor Nephrin and its cytoplasmic partners, Nck and N-WASP. With Nephrin attached to the bilayer, multivalent interactions enable these proteins to polymerize on the membrane surface and undergo two-
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