Encoding mechanical information through multimolecular structures: Lessons from directed cell migration
Seminar by Vinay Swaminathan
from Wallenberg Center for Molecular Medicine Fellow, Lund University
Interactions between cells and their mechanical environment is a critical regulator of important physiological functions that gets hijacked in diseases such as cancer. One such function is directed cell migration where cells sense physical cues such as stiffness, varying topologies and fluid flow and migrate directionally in response. While we know relatively a lot about how individual molecules respond to forces, we still lack the understanding of how these “force-sensitive” proteins come together to function in a cell to allow it to sense and transmit mechanical information critical for function. In this seminar, I will first discuss the mechanical cues a cell in our body encounters and their role in normal physiology and disease. I will then introduce the primary subcellular structure that mediates interactions between the cell and its mechanical environment- Integrin-based focal adhesions. I will then describe in detail my recent findings on how integrin receptors come together in focal adhesions and act as mechanical compass where the 3-dimensional orientation of these receptors is sensitive to the magnitude and directionality of mechanical information and thus encodes it. I will also describe the unique microscopy technique that facilitated the discovery of this novel molecular organization and bridges the gap between crystal structures and resolution-limited microscopy. I will conclude by looking ahead to what such an organization of molecules tells us about building mechano-sensitive structures in cells, how we can test its role and perturb it during cell function and how this will provide us with novel insights into diseases such as cancer and immune-disorders.
Time: 1 April 2019, 15:00