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Cellular mechanotransduction: role of the nucleus
Cells exploit traction forces to sense the physical characteristics of their
microenvironments, which co-regulates a variety of cellular processes like stem cell
differentiation, development and cancer progression. Mechanical forces, rising from the
extracellular environment or from the contractile cell cytoskeleton, can be transmitted to the cell
nucleus as the cytoskeleton physically couples the cell periphery to the nuclear envelope. These
forces are converted into biochemical activity in a mechanotransduction process, where
mechanical forces alter the protein structure, exposing cryptic binding sites.
Nuclear lamina plays a key role in the nuclear mechanotransduction, since it resides in the
interface between the cytoplasm and the inner nucleus. The nuclear lamina is composed of a 10–
60 nm thick protein layer beneath the inner nuclear membrane and its major constituents are Aand B-type lamins. Lamins are involved in the regulation of gene expression and control the
mechanical stability of the nucleus. However, relatively little is known about mechanoregulation
and mechanosensitivity of lamin proteins.
In my talk, I will discuss the recent discoveries regarding the nuclear mechanotransduction
and its potential role in the control of gene expression. I will show how mechanical forces can lead
into re-organization of the nuclear lamina. This re-organization of the lamina is promoted by
compressive forces, emerges during cell spreading, and requires lamin protein multimerization,
intact nucleoskeleton–cytoskeleton linkages and proper assembly of actin fibers. These findings
help to decipher how the physical properties of cellular microenvironments can regulate nuclear
events and gene expression.