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Col·loquis FMC: Sergi Garcia-Manyes
We are pleased to have Sergi Garcia-Manyes as our next speaker for the Department's Colloquium entitled "Single molecule insights into cellular mechanotransduction".
Single molecule insights into cellular mechanotransduction
Prof. Sergi Garcia-Manyes
Randall Centre for Cell and Molecular Biophysics &eamp; Department of Physics -- King's College London, United Kingdom
Cellular mechanostransduction relies on the conversion of mechanical cues into chemical signals, which propagate from the focal adhesion hub through the cytoskeleton to ultimately reach the nucleus through the Nuclear Pore Complex (NPC), and switch on specific force-dependent transcriptional programmes. However, how cellular mechanotransduction is regulated by the nanomechanical properties of the underpinning force-bearing proteins remains largely unknown. Here we first used a newly developed single-molecule magnetic tweezers combined with UV-light to demonstrate that oxidation of a previously cryptic methionine in the talin mechanosensor impairs vinculin binding. When translating the single-molecule findings into the cellular context, we found a loss in talin/vinculin co-localisation at focal adhesions of NIH3T3 mouse fibroblasts when exposed to µM concentrations of H2O2 and a decrease in the nuclear localisation of the YAP transcription factor (TF). In this vein, how the nuclear shuttling of mechanosensitive TFs is regulated by their mechanical properties remains also unclear. By using a combination of single-molecule mechanics and single-cell optogenetics, we discovered that proteins with locally soft regions in the vicinity of the nuclear-localization sequence exhibit higher nuclear-import rates. Inspired by these findings, we designed a short and easy-to-express unstructured peptide tag that accelerates the nuclear-import rate of stiff protein cargos. Altogether, our cross-scale experiments provide a single molecule perspective onto cellular mechanotransduction.
Dr Sergi Garcia-Manyes is Professor of Biophysics at King's College London and a Principal group leader at the Francis Crick Institute, where he also serves as an assistant Research Director. At King's he holds a joint appointment between the Randall Centre for Cell and Molecular Biophysics and the Department of Physics, where he is the Head of the Biological Physics and Soft Matter (BPSM) research group. Dr. Garcia-Manyes obtained his PhD in Physical Chemistry from the University of Barcelona, and conducted his postdoctoral training in the field of single molecule mechanics in the Biology Department of Columbia University in the City of New York. Dr. Garcia-Manyes' lab is interested in mechanobiology across different length-scales, spanning from single molecules to individual cells, with a particular accent on the molecular mechanisms underpinning mechanical folding of single mechanosensory proteins and protein mechanochemistry at the single bond level. Dr. Garcia-Manyes has been awarded the Spanish Biophysical Society Award, the British Biophysical Society Award, and the Leverhulme Research Leadership Award. He was awarded a Royal Society Wolfson Fellowship, and he currently holds a Wellcome Trust Investigator Award and an ERC Advanced grant.
