Role of the mechanical micro-environment in early stages of cadherins junction formation
Final Report Abstract
Receptors residing on the plasma membrane, are instrumental in the adhesion of cells in a variety of tissues. Typically, they aggregate into micron size domains, in the environment comprising the glycocalyx, the plasma membrane and the cytoskeleton. As they mature, the adhesive contacts often attach to actin through unique macromolecular complexes. Upon the establishment of nano-clusters, different morphology and dynamics of growth of adhesions are regulated by fine changes in membrane dynamics. Past studies by us and others have established that beside the biochemical regulation emphasized in the past for cells, phenomena associated with the fluctuating membrane microenvironment, as well as glycocalyx, competitive binders and ligand mobility provides mechanical control parameters for the development of adhesions. The relevance of this mechanical milieu remained disputed in the context of cells. The aim of this proposal was to resolve this debate by elucidating the relative roles of specific and generic interactions, and provide a deeper understanding of the dynamics of the aggregation and binding of cadherins, and other adhesion proteins, related to the activity of the cell. Building on our excellent track record in adhesion, we aimed to address this goal by improving on the state-of-the-art synthetic models based on vesicles and cells, and studying them with top of the range experimental techniques. Sophisticated imaging, data analysis, supported by comprehensive theoretical modelling was conceived to provide a sound conceptual framework to understand the early stages of the cadherin and other protein-based formation of adhesive nano-cluster and its mechanical regulation.
Publications
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Recent Advances and Prospects in the Research of Nascent Adhesions. Frontiers in Physiology, 11.
Henning, Stumpf Bernd; Ambriović-Ristov, Andreja; Radenovic, Aleksandra & Smith, Ana-Sunčana
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Biomechanics as driver of aggregation of tethers in adherent membranes. Soft Matter, 17(44), 10101-10107.
Li, Long; Kamal, Mohammad Arif; Stumpf, Bernd Henning; Thibaudau, Franck; Sengupta, Kheya & Smith, Ana-Sunčana
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Ligand Nanocluster Array Enables Artificial-Intelligence-Based Detection of Hidden Features in T-Cell Architecture. Nano Letters, 21(13), 5606-5613.
Nassereddine, Aya; Abdelrahman, Ahmed; Benard, Emmanuelle; Bedu, Frederic; Ozerov, Igor; Limozin, Laurent & Sengupta, Kheya
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Molecular Biomechanics Controls Protein Mixing and Segregation in Adherent Membranes. International Journal of Molecular Sciences, 22(7), 3699.
Li, Long; Stumpf, Bernd & Smith, Ana-Sunčana
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Protein induced lipid demixing in homogeneous membranes. Physical Review Research, 3(4).
Stumpf, Bernd Henning; Nowakowski, Piotr; Eggeling, Christian; Maciołek, Anna & Smith, Ana-Sunčana
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First-Principle Coarse-Graining Framework for Scale-Free Bell-Like Association and Dissociation Rates in Thermal and Active Systems. Physical Review X, 12(3).
Janeš, Josip Augustin; Monzel, Cornelia; Schmidt, Daniel; Merkel, Rudolf; Seifert, Udo; Sengupta, Kheya & Smith, Ana-Sunčana
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Physics of Organelle Membrane Bridging via Cytosolic Tethers is Distinct From Cell Adhesion. Frontiers in Physics, 9.
Kamal, Mohammad Arif; Janeš, Josip Augustin; Li, Long; Thibaudau, Franck; Smith, Ana-Sunčana & Sengupta, Kheya
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Demixing of homogeneous binary lipid membranes induced by protein inclusions. Physical Review E, 107(5).
Nowakowski, Piotr; Stumpf, Bernd Henning; Smith, Ana-Sunčana & Maciołek, Anna
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Membrane Fluctuation Model for Understanding the Effect of Receptor Nanoclustering on the Activation of Natural Killer Cells through Biomechanical Feedback. Nano Letters, 24(18), 5395-5402.
Pandey, Ashish; Nowakowski, Piotr; Ureña, Martin Carlos; Abu, Ahmad Muhammad; Edri, Avishay; Toledo, Esti; Tzadka, Sivan; Walther, Jonas; Le Saux, Guillaume; Porgador, Angel; Smith, Ana-Sunčana & Schvartzman, Mark
