Deciphering the role of surface mechanics during cell division

Introduction

Cell division is fundamental for all life forms and its dysregulation can lead to severe diseases including cancer. The dramatic shape changes eukaryotic cells have to undergo to divide are mostly driven by the cell surface, a complex system that can dynamically modify its mechanical properties.

Importance of Physical Cues

While the importance of physical cues for cell division has long been recognized, the lack of specific tools that modify particular physical properties and bridge molecular-to-cellular scale biophysics prevents us from understanding how cells use their mechanics to regulate form and function.

New Molecular Tools

To address this, my group has recently developed a new class of molecular tools that for the first time allows us to manipulate surface mechanics specifically and acutely in living cells. Exploiting this powerful new structural biophysics approach, our first discoveries excitingly demonstrate that:

1. The strength of tethering between the plasma membrane and the cortical cytoskeleton is a key control mechanism for cell division.
2. This mechanism is relevant both in cultured cells as well as in mouse embryos.

Project Goals

The overarching goal of MitoMeChAnics is to systematically understand how cell surface mechanics controls the different steps of division. My team and I will systematically and quantitatively link cell surface architecture with the resulting mechanics and morphology to determine the structure-function relationship at the cellular periphery in space and time.

Methodology

To this end, we will:

• Deploy novel molecular tools.
• Combine them with cellular biophysical measurements, super-resolution microscopy, and in situ cryo-electron tomography.
• Build data-driven theoretical models to unravel the physical principles that control the membrane-cortex interface.
• Test their predictions with novel optogenetic tools.

Interdisciplinary Approach

Our project thus takes a highly interdisciplinary approach, combining mechanobiology, molecular engineering, structural analysis, and theory to decipher how cells use their mechanics to control mitosis.