MOTILECELLBIOPHYSICS · Biophysical Aspects of Actin-Based Motility- An Integrative Whole-Cell Analysis

Biophysical Aspects of Actin-Based Motility - An Integrative Whole-Cell Analysis

This project focused on actin-based cell movement which is one of the prime examples of biological self-organization. Actin-based motility is crucial for a wide range of biological phenomena such as defense against injury or infection, embryogenesis and cancer metastasis. From the physical point of view, the actin machinery is a far-from-equilibrium system of semi-flexible filaments and auxiliary proteins which self-organizes into a myriad of dynamic structures. The molecular players involved in actin-based movement and the basic biochemical mechanisms are largely known. However, the principles governing their self-organization, which involve an intricate interplay between biophysical and biochemical processes, are still poorly understood. The research has focused on understanding this remarkable self-organization. Working on fish keratocytes as a relatively simple model system we have characterized the role of the interplay between the actin cytoskeleton and the cell membrane in the motility process. We measured membrane tension in moving cell under various conditions, and showed that tension is largely determined by the balance between cytoskeletal forces and the cell membrane. Importantly, membrane tension can induce mechanical coupling between processes occurring at distal locations along the cell boundary. As such, we showed that tension is crucial for coupling protrusion at the front with retraction at the rear, and thus plays a central role in large-scale coordination of cellular dynamics. In parallel to our research on actin-based movement of live cells, we have invested substantial efforts to develop artificial model systems which emulate cellular actin dynamics in a more controlled and well-defined manner. We have developed a reconstituted system that self-organizes into dynamic actin cortices at the inner interface of water-in-oil emulsions. We have shown that this artificial system undergoes spontaneous symmetry breaking, driven by myosin-induced cortical actin flows, which appears remarkably similar to the initial polarization of the embryo in many species. The artificial cortices recapitulate the rich dynamics of actin cortices in vivo, revealing the basic biophysical and biochemical requirements for cortex formation and symmetry breaking. Our research promotes quantitative understanding of cell motility mechanisms and more generally on the understanding of the interplay between molecular processes, regulatory pathways and biophysical forces in biological self-organization. Our work will serve as a starting point for understanding the motile behavior of more complex cells such as cancer cells and gaining mechanistic understanding of their behavior. As such, our work can have important implications for biomedical research; quantitative understanding of the mechanochemical dynamics of the actin cytoskeleton in cancer cells has the potential to inform the design of anti-metastasis cancer drugs. Moreover, our work on the development of artificial cells can inspire the development of biomimetic systems for bioengineering and nanotechnological applications.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз