|Date(s):||14 March 2018|
|Time:||15:30 - 16:00|
|Location:||David Sizer Lecture Theatre, Bancroft Building, Mile End Campus|
Mechanical properties are cues for many biological processes. We are investigating how these properties affect the cardiovascular health, thereby focusing on two cell types: cardiomyocytes and vascular smooth muscle cells (VSMCs).
Dr Thomas Iskratsch
In the heart, changes to the extracellular matrix composition and cross-linking results in stiffening of the cellular microenvironment during development. However, myocardial infarction and cardiomyopathies lead to fibrosis and an even stiffer environment. Our work is exploring how cardiomyocytes are sensing these changes, which can trigger responses from differentiation to de-differentiation, or cell death.
VSMCs on the other hand play a central role in the onset and progression of atherosclerosis or vascular injury, where their migration, matrix secretion, or degradation functions are deregulated. Enhanced matrix stiffness causes a switch of VSMCs from a contractile to a synthetic phenotype. This switch is significantly enabled by the formation of podosomes, integrin-rich adhesive, mechanically protrusive structures at the matrix interface of the plasma membrane. In VSMCs, we identified that podosome formation is regulated by a mechanical feedback mechanism, which we are now investigating in detail.
To study the mechanical sensing of cardiomyocytes and VSMCs we use tools to measure cellular forces, such as nanopillar arrays or molecular tension sensors, high throughput image analysis, as well as live cell and super-resolution microscopy.
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