Seminar Prof. Dr. Tamara Bidone - Multiscale models of integrin and integrin adhesions: from all-atom to macromolecular and mesoscale simulations
Decanato - Facoltà di scienze biomediche
Data: 9 Giugno 2023 / 14:30 - 15:30
D.1.15, Campus Est
Integrins are single pass alpha/beta heterodimeric transmembrane receptors that physically connect the extracellular matrix to the cell cytoskeleton, thus integrating internal and external environments. Integrins undergo dynamic transitions from bent (inactive) to extended (active) conformations, which correspond to an increase in ligand binding affinity and adhesions assembly. These structural transitions require a remarkable convergence of interactions and influences. Signals from the external, internal and transmembrane environments interplay for integrin activation, but their exact role remains largely elusive. In my lab, we combine modeling approaches at different length and time scales to evaluate the effects of force and lipid membranes on the slow dynamics of integrin receptors and their role in conformational activation, adhesion assembly and membrane protrusions. In this talk, I will present our new results from steered molecular dynamics simulations and time independent component analysis, revealing that the beta leg of integrin senses mechanical forces through slow motions in the direction of extension. These effects occur only when integrin is embedded in a membrane bilayer. Results from Brownian dynamics simulations also reveal that crowded membranes promote the clustering of integrins, especially when they transition into extended conformations within crowded regions, such as lipid rafts. Our models also show that integrin conformational activation is correlated with the efficiency of membrane protrusion, which is important for directed cell motion. Collectively, our results from multiscale modeling support a picture in which conformational changes of integrin modify adhesion assembly to control cell activity.
It will also be possible to attend remotely via Teams at this link: https://teams.microsoft.com/l/meetup-join/19%3ameeting_NGI2YjBiYzYtZTVkNC00NmZhLWI0ZTItMmVmOWFiZTg1MTk5%40thread.v2/0?context=%7b%22Tid%22%3a%2295bdc5ac-afb5-4881-801b-3874f365cd6f%22%2c%22Oid%22%3a%22ee90bfd0-f41b-49f3-bd2a-55bded28358a%22%7d
Prof. Tamara Bidone is Assistant Professor of Biomedical Engineering and Adjunct Assistant Professor of Biochemistry and of Molecular Pharmaceutics at University of Utah, USA, within the department of Biomedical Engineering and the Scientific Computing and the Imaging Institute. Her research involves the combination of cell and molecular biomechanics, biophysics, and computational biology.
Prof. Dr. Bidone conducted postdoctoral research from 2013-2016 at Lehigh University in the department of physics, with Dimitrios Vavylonis as her advisor. She held another postdoctoral research associate position at the University of Chicago department of Chemistry from 2016-2018, with Gregory A. Voth as an advisor. She began her instructing career at Lehigh University in 2015, teaching a computational physics course. She currently is an Assistant Professor of Biomedical Engineering at the University of Utah. Her most significant contribution to research to date is her development of new simulation methods to understand and sample conformational transitions in proteins under tension and mechanical stimuli . Additionally, through her research, she has significantly contributed to the understanding of how both molecular interactions and states affect mesoscale and cellular level systems. This work is highlighted in her research on multiscale modeling at the threshold of cellular and molecular phenomena . She has applied these modeling techniques to problems related to engineering on the cellular and tissue level, such as the effect of the extracellular matrix on cell spreading .
1. Bidone, T. C., et al. (2019). Coarse-Grained Simulation of Full-Length Integrin Activation. Biophysical Journal,116(6), 1000-1010. doi:10.1016/j.bpj.2019.02.011
2. Deriu MA, Shkurti A, Paciello G, Bidone TC, Morbiducci U, Ficarra E, Audenino A & Acquaviva A (2012). Multiscale modeling of cellular actin filaments: from atomistic molecular to coarse-grained dynamics. Proteins. Vol. 80, 1598-609.
3. Oakes PW, Bidone TC, Beckham Y, Skeeters AV, Ramirez-San Juan GR, Winter SP, Voth GA & Gardel ML (2018). Lamellipodium is a myosin-independent mechanosensor. Proceedings of the National Academy of Sciences of the United States of America. Vol. 115, 2646-2651.