The nanoscale regulation of cell surface mechanics

The Paluch lab investigates how cells control their shape and the underlying cellular mechanical properties. The project will focus on the actomyosin cortex, a thin cytoskeletal network that supports the plasma membrane. Myosin-generated contractility at the cell cortex controls cell surface mechanics and drives cellular deformations. Recently, through super-resolution microscopy approaches, we have shown that in interphase cells, myosin minifilaments are positioned at the cytoplasmic side of the actomyosin cortex. Upon mitotic entry, myosin minifilaments penetrate the actin cortex as cortical tension drastically increases. How this increase, crucial for the success of cell division, is controlled is not understood. We hypothesize that the cortex is structurally poised for rapid tension changes, and that tuning actin network nanoscale architecture can lead to abrupt changes in the overlap of actin and myosin at the cortex. Myosin entry into the cortex upon mitosis entry would thus be akin to a phase transition in cortex organisation.

To address this hypothesis, we will explore the 3D nanoscale architecture of myosin minifilaments at the cortex. Using Structured Illumination Microscopy, we aim to gain a single molecule understanding of the dynamic behaviour of myosin minifilaments at the onset of mitosis. We will then use Electron Microscopy to interrogate the ultrastructure of the actomyosin cortex, which together with our light microscopy data, will uncover how nanoscale processes control global cell mechanics.  

Key reference: 
Truong Quang BA, Peters R, Cassani DAD, Chugh P, Clark AG, Agnew M, Charras G, Paluch EK. Extent of myosin penetration into the actin cortex regulates cell surface mechanics. (2021) Nat Comm. 12:6511.