Friday, October 3, 2025 10/3/2025

Mechanotransduction via LIM Domain Protein Mechanosensing

Award Number: R01GM148644
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

Group Awards By:

View Award Description

Mechanotransduction via LIM Domain Protein Mechanosensing - Project Summary Mechanical interactions play a fundamental role in physiology, allowing cells to move, generate forces, and assemble into multicellular structures. Key to these processes is the ability of cells to turn mechanical signals into biochemical signals, an activity known as mechanotransduction. The search for mechanosensitive proteins that could facilitate mechanotransduction has primarily focused on proteins that undergo conformational changes in response to force or proteins that display changes in the bond kinetics under load. There exists another class of proteins, however, that recognize structures under strain. The canonical example of this class of proteins is the LIM domain protein zyxin, which recognizes strained actin stress fibers and recruits actin polymerization factors to repair them. Recent work has highlighted that the strain sensing mechanism of the LIM domains is not unique to zyxin and that numerous other members of the family of LIM domain proteins display a similar ability. This suggests LIM domain proteins could act as mechanotransducers, recognizing strain via their LIM domains and converting it to other biochemical signals via interactions with the other domains in the protein. To explore this hypothesis further it is crucial that we understand how LIM domains recognize strained actin filaments, and how those interactions propagate signals downstream of the strain sites. Here we propose to establish rigorous experimental strategies to decipher the mechanisms underlying LIM domain protein mechanotransduction. We employ a combination of biophysical techniques including laser ablations, optogenetics and cell stretching to quantitatively and repeatedly induce strain sites in the actin cytoskeleton. In Aim 1 we will test alternative mechanisms of LIM domain strain sensing by comparing proteins from the testin family of LIM domain proteins which require only a single LIM domain to recognize strain sites, compared to the three tandem LIM domains that zyxin requires. In Aim 2 we will test whether in addition to stretched actin filaments in stress fibers, LIM domain proteins can recognize other strained actin structures, such as compressed stress fibers or actin meshworks. Finally, in Aim 3 we will investigate how binding of LIM domain proteins to strain sites leads to a propagation of that mechanical signal to other parts of the stress fiber and the extracellular matrix. Together these studies will greatly expand our knowledge of mechanotransduction and provide insight into this fundamental signaling mechanism.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $306,821 )
2025	2025	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	3	7/25/2025	NON-COMPETING CONTINUATION	$306,821
														Subtotal = $306,821

Issue Date FY: 2024 ( Subtotal = $306,821 )
2024	2024	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	2	7/24/2024	NON-COMPETING CONTINUATION	$306,821
														Subtotal = $306,821

Issue Date FY: 2023 ( Subtotal = $306,821 )
2023	2023	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Biomedical Research and Research Training	000	1	8/24/2023	NEW	$306,821
														Subtotal = $306,821

Grand Total All Awards = $920,463

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanotransduction via LIM Domain Protein Mechanosensing

Award Number: R01GM148644

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer