[R01] Structure, function, and mechanobiology of a compression-sensitive cell-cell junction
Ente: National Heart Lung and Blood Institute
Scadenza: 2029-05-31
Importo max: 615.739 EUR
Paese: US
Descrizione
Project Description and Summary
The goal of this proposal is to characterize a newly identified cadherin-mediated cell-cell junction, and
understand the contexts in which it functions. The cooperation between adhesions and mechanical forces is a
central regulator of many developmental and homeostatic processes that has been studied for over half a
century across a wide variety of biological contexts. In particular, the assembly of junctional complexes
triggered by mechanical tension – a phenomenon known as adhesion strengthening – is widely conserved
across a diverse range cell-matrix and cell-cell adhesion receptors, such that it has been suggested that it may
be the only type of response in present day living systems. However, the investigator has recently discovered a
cadherin-mediated cell-cell junction that is characterized by a distinct composition and the ability to assemble
in response to compressive forces. Here, the investigator will identify the molecular components,
organizational structure, underlying force-responsive mechanisms, and cellular impact of this previously
unappreciated junctional complex, and elucidate the biological contexts in which this pathway is engaged.
These objectives will be achieved through an interdisciplinary research effort built around three Aims: Specific
Aim 1 will be to define the structure and molecular participants of this compression sensitive, cadherin-
mediated cell-cell junction. Specific Aim 2 will investigate the molecular mechanisms, mechanics, and
dynamics regulating the cell-cell junction. Specific Aim 3 will be to explore the extent to which these junctions
contribute to a range of biological contexts where junctions are known to be important, including lymphatic
drainage function and sorting morphogenesis. Together, these studies will offer critical insights into an
important new type of cell-cell junction that uniquely assembles with compression, and thereby add a new
chapter in cell adhesion biology.
Istituzione: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
PI: CHRISTOPHER S CHEN
Progetto: 5R01HL175072-02
Settori: National Heart Lung and Blood Institute
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