Cell biophysics | EPFL Graph Search

Cell biophysics (or cellular biophysics) is a sub-field of biophysics that focuses on physical principles underlying cell function. Sub-areas of current interest include statistical models of intracellular signaling dynamics, intracellular transport, cell mechanics (including membrane and cytoskeletal mechanics), molecular motors, biological electricity and genetic network theory. The field has benefited greatly from recent advances in live-cell molecular imaging techniques that allow spatial and temporal measurement of macromolecules and macromolecular function. Specialized imaging methods like FRET, FRAP, photoactivation and single molecule imaging have proven useful for mapping macromolecular transport, dynamic conformational changes in proteins and macromolecular interactions. Super-resolution microscopy allows imaging of cell structures below the optical resolution of light. Combining novel experimental tools with mathematical models grounded in the physical sciences has enabled significant recent breakthroughs in the field.

The Caenorhabditis elegans protein SAS-5 forms large oligomeric assemblies critical for centriole formation

Pierre Gönczy, Georgios Hatzopoulos, Nicola Jane Dynes, Sheng Kai Pong

Centrioles are microtubule-based organelles crucial for cell division, sensing and motility. In Caenorhabditis elegans, the onset of centriole formation requires notably the proteins SAS-5 and SAS-6, which have functional equivalents across eukaryotic evolution. Whereas the molecular architecture of SAS-6 and its role in initiating centriole formation are well understood, the mechanisms by which SAS-5 and its relatives function is unclear. Here, we combine biophysical and structural analysis to uncover the architecture of SAS-5 and examine its functional implications in vivo. Our work reveals that two distinct self-associating domains are necessary to form higher-order oligomers of SAS-5: a trimeric coiled coil and a novel globular dimeric Implico domain. Disruption of either domain leads to centriole duplication failure in worm embryos, indicating that large SAS-5 assemblies are necessary for function in vivo.

2015

Force Transmission in Migrating Cells

Maxime Fred Maurice Fournier

Ability to migrate is a fundamental property of all animal cells. Cell migration underlies such important physiological and pathological processes as embryonic development, immune response, tissue regeneration and cancer metastasis. As cell migration involves forces and motion, it is ultimately a physical phenomenon that should be understood in terms of fundamental physical laws. Cell migration mechanisms are based on the activity of the cytoskeleton, a system of intracellular filaments and motor proteins. During cell migration, forces developed by the cytoskeleton are transmitted, through specific adhesions complexes, to the substrate. Composition and dynamics of the cytoskeleton has been subject of many studies, but it remains poorly understood how the cytoskeleton reactions and its interaction with extra cellular matrix are orchestrated to result in coordinated migration behavior. The main part of this thesis consists of the experiments and analysis of force transmission during cell migration in the experimental system of fish epidermal keratocytes. Our experimental approaches involved microinjection for proteins dynamics quantification, micromanipulation, use of compliant substrate, simultaneous imaging of cytoskeleton and substrate deformation, and the use of cytoskeletal inhibitors. In parallel with the experiments, significant computational work has been performed to program and adapt existing algorithms to analyze experimental data. Thanks to the combination of our experimental and computational approaches, we were able to correlate actin dynamics and traction forces over the whole cell, to map the efficiency of force transmission, and to reveal slipping and gripping mechanisms differentially involved in stress transmission in different parts of the cell. We also investigated contributions of actin assembly and myosin-dependent contractility to force generation and provided evidence that cell translocation could be powered by two different engines. Additionally, we performed micromanipulation experiments to identify the cell polarity cues associated with specific cytoskelatal reactions and regions of the cell. We have also collaborated with the laboratory of one of the leading modellers in the field of cell biophysics to validate a new mathematical model of cell migration and force transmission.

EPFL2011