‘form follows function follows form’
Overview
Cells carry out various physiological processes essential for its survival and survival of the organism that it is a part of. Many of these processes such as division, adhesion, migration, endocytosis, death etc require precise and characteristic changes to the cellular shape and architecture. This, in turn, requires remodeling of the cytoskeleton (actin, microtubules, intermediate filaments) as well as deformation of the cell surface. While considerable work has been carried out in understanding how cytoskeleton regulates cell shape, the cell cortex is mostly unexplored. That is what we are interested in!
The cell cortex, a thin layer (100~200 nano meters i.e 0.000000001 metres ) of protein mesh juxtaposed to the inner leaflet of the plasma membrane, determines the properties of the cell surface. Composed predominantly of filamentous actin( F-actin), myosin motors, and many actomyosin regulating proteins, the cortex provides the essential mechanical support to the overlying plasma membrane.
Variety of forces - both internal and external, impinge on the cell surface. The cortex, on one hand, enables cells to resist these stresses and on the other hand, directs changes in the shape of cell surface by generating compressive forces through actomyosin contractility. How the surface deforms under the influence of these forces would depend on the material properties (such as visco-elasticity & contractile tension) of the cortex.
We know that biochemical pathways regulate cortex mechanics during individual cellular processes, thereby coupling cellular processes with appropriate shape deformations. But how is the cell able to actively sense, process and respond to different signaling pathways that alter the cortex to bring about a change in the cell shape?
We do not fully understand it, yet.
Cells carry out various physiological processes essential for its survival and survival of the organism that it is a part of. Many of these processes such as division, adhesion, migration, endocytosis, death etc require precise and characteristic changes to the cellular shape and architecture. This, in turn, requires remodeling of the cytoskeleton (actin, microtubules, intermediate filaments) as well as deformation of the cell surface. While considerable work has been carried out in understanding how cytoskeleton regulates cell shape, the cell cortex is mostly unexplored. That is what we are interested in!
The cell cortex, a thin layer (100~200 nano meters i.e 0.000000001 metres ) of protein mesh juxtaposed to the inner leaflet of the plasma membrane, determines the properties of the cell surface. Composed predominantly of filamentous actin( F-actin), myosin motors, and many actomyosin regulating proteins, the cortex provides the essential mechanical support to the overlying plasma membrane.
Variety of forces - both internal and external, impinge on the cell surface. The cortex, on one hand, enables cells to resist these stresses and on the other hand, directs changes in the shape of cell surface by generating compressive forces through actomyosin contractility. How the surface deforms under the influence of these forces would depend on the material properties (such as visco-elasticity & contractile tension) of the cortex.
We know that biochemical pathways regulate cortex mechanics during individual cellular processes, thereby coupling cellular processes with appropriate shape deformations. But how is the cell able to actively sense, process and respond to different signaling pathways that alter the cortex to bring about a change in the cell shape?
We do not fully understand it, yet.
Objectives
Our long-term goal is to understand how the actomyosin cortex is regulated to allow cells to deform accurately while carrying out various physiological activities. Many questions remain to be asked and answered before we get there, such as
Our long-term goal is to understand how the actomyosin cortex is regulated to allow cells to deform accurately while carrying out various physiological activities. Many questions remain to be asked and answered before we get there, such as
- How is/are the material properties of cell cortex altered during various physiological processes (for e.g cell division, endocytosis or pathogenic infection)?
- Does a cell sense such changes to its cortex? If it does, then how does it calibrate its response?
- How does this alteration result in a characteristic cell shape change?
Approach
We chose C. elegans as the model organism to investigate actomyosin cortex regulation. It is easily maintained, extremely amenable to genetic manipulation and optically transparent. We employ genetic tools, genome editing techniques (such as CRISPR) and live & quantitative confocal fluorescence microscopy to interrogate the cortex dynamics in various actomyosin systems of C. elegans.
We chose C. elegans as the model organism to investigate actomyosin cortex regulation. It is easily maintained, extremely amenable to genetic manipulation and optically transparent. We employ genetic tools, genome editing techniques (such as CRISPR) and live & quantitative confocal fluorescence microscopy to interrogate the cortex dynamics in various actomyosin systems of C. elegans.
Significance
The actomyosin cortex plays a critical role in governing every aspect of cell and tissue morphogenesis. Investigating how it is regulated during distinct cellular processes has broad implications for understanding developmental defects and diseases in humans. In spite of this very little is known about the mechanics of actomyosin cortex in-vivo. Our research efforts are directed towards bridging this knowledge gap.
The actomyosin cortex plays a critical role in governing every aspect of cell and tissue morphogenesis. Investigating how it is regulated during distinct cellular processes has broad implications for understanding developmental defects and diseases in humans. In spite of this very little is known about the mechanics of actomyosin cortex in-vivo. Our research efforts are directed towards bridging this knowledge gap.
© Anup Padmanabhan 2023