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4-Mechanotransduction Via Cell Substrate Adhesions

Mechanotransduction involves the process of actin treadmilling, where actin filaments grow at one end while shrinking at the other, facilitated by proteins like cofilin and profilin. In migrating cells, actin polymerizes at the leading edge and flows retrograde, with focal adhesions providing traction for movement. Cells also exhibit durotaxis, migrating preferentially towards stiffer substrates due to better spreading and alignment of actin stress fibers.

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11 views9 pages

4-Mechanotransduction Via Cell Substrate Adhesions

Mechanotransduction involves the process of actin treadmilling, where actin filaments grow at one end while shrinking at the other, facilitated by proteins like cofilin and profilin. In migrating cells, actin polymerizes at the leading edge and flows retrograde, with focal adhesions providing traction for movement. Cells also exhibit durotaxis, migrating preferentially towards stiffer substrates due to better spreading and alignment of actin stress fibers.

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junkemail4megha
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We take content rights seriously. If you suspect this is your content, claim it here.
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Mechanotransduction

Actin treadmilling

Treadmilling is a phenomenon observed within protein filaments of the cytoskeletons of many cells, especially in
actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks,
resulting in a section of filament seemingly "moving" across a stratum or the cytosol.

This is due to the constant removal of the protein subunits from these filaments at one end of the filament, while
protein subunits are constantly added at the other end

Cofilin and profilin are two major effector molecules involved in actin treadmilling. Cofilin functions by binding to ADP-
actin on the negative end of the filament, destabilizing it, and inducing depolymerization. Profilin induces ATP binding
to G-actin so that it can be incorporated onto the positive end of the filament.

https://www.youtube.com/watch?v=VVgXDW_8O4U
Nascent and mature focal adhesions

https://www.youtube.com/watch?v=RswLllKV5-0
Actin retrograde flow and cell traction

In a migrating cell, actin filaments polymerize at the


leading edge, and flow back into the body of the cell
(retrograde flow).

Focal adhesions (FAs)—the cell's tether points to the


extracellular matrix (ECM)—forming at the cell's
leading edge provide handholds for the flowing actin
that impede actin's retrograde movement, and in so
doing create the traction needed to push the cell
forward.

At the frontal tip (where FAs are small), actin


retrograde flow was rapid and traction was minimal.
A little farther back in the leading edge (where FAs
are bigger), traction increased and actin speeds
slowed. Back toward the cell body, however, despite
actin speeds dropping below 8–10 nm per second,
the FAs exerted less traction.

the switch occurs roughly in the area where the


lamellipodia (leading edge) ends, and the cell body
https://www.youtube.com/watch?v=xtpaymWR22E
begins.
Actin retrograde flow and cell traction
Durotaxis- ability of cells to migrate preferentially towards stiff substrate
Durotaxis- ability of cells to migrate preferentially towards stiff substrate
Why do cells migrate better on stiffer substrates?
Soft Stiff
Better spreading
(Focal adhesion staining)

Actin stress fiber alignment

Actin

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