Analysis of traction forces and intracellular mechanics in aggregates of endothelial and stromal cells

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Author's e-mailalice1.savoia
mail.polimi.it

Document typeMaster thesis
Date2022-01-27
Rights accessOpen Access
Except where otherwise noted, content on this work
is licensed under a Creative Commons license
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Attribution-NonCommercial-NoDerivs 3.0 Spain
Abstract
Animal cells sense and transduce physical forces. In everyday physiological activities,
tissues composed by groups of cells interacting together can stretch significantly, for
instance when heart pumps, or lung inflate during breathing. Evidence also show that
altered cell mechanosensing and mechanotransduction occurs in pathologies, such as
cancer.
These cell mechanics events can be studied in simplified 2D in vitro systems, where forces
exerted by cells are measured with accuracy. One commonly used technique is 2D traction
force microscopy (TFM), which makes use of high-resolution microscopy and
fluorescently decorated elastic culture substrates to measure the substrate displacement
caused by cell forces. In a previous study, we have built on analysis pipelines that convert
displacement into tractions, to further obtain computationally the intracellular
(cytoskeletal) structural organization that could give rise to such forces, starting from TFM
data on single cells. For that, we have solved an elastic minimization problem assuming
that intracellular stresses are propagated in cable-like elements and seeking a mechanical
equivalence leading to the experimentally measured tractions. However, our previous work
and other research in experimental literature have not focused on more realistic situation,
such as intracellular organization when multiple cell types are interacting.
Our experiments show that distinct cell types, endothelial and fibroblasts exert different
level of forces on the substrate. Moreover, by varying the stiffness of the substrate, we
measured an increase of the spreading area for both endothelial cells and fibroblasts, as
stiffness increases, up to a plateau. Finally, as a proof of concept, we obtained
computationally the intracellular organization for a case of traction field produced by
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several endothelial cells interacting and observe a possible mechanical communication
between cells by transmission of intracellular forces.
DegreeMOBILITAT INCOMING
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