2413064
Project Grant
Overview
Grant Description
NSF-ANR MCB/PHY - MECHALINC: Mechanistics of LINC-mediated force transmission.
Cells receive many signals from their environment, including tensions and mechanical forces that are transferred all the way down to their nucleus.
Nuclear shape adaptations to those forces are critical for cell fate and function.
Yet, the physical and molecular principles underlying those adaptive mechanisms remain largely undefined.
By integrating state-of-the-art scientific approaches, this project will generate mechanistic understandings of nuclear mechanics and predictive insights into the organization of force-transmitting complexes in human cells.
The work will offer novel rationales to design bio-inspired and force-responsive nanodevices for human health.
It will also contribute new perspectives on the normal and defective mechanobiology of the nucleus, advancing our understanding of those critical cellular processes and the diseases that are caused by dysfunction in these systems.
A key aspect of the project is the training of early-career scientists, graduate students, undergraduates, and STEM-focused high school students to expose them to a unique research experience at the crossroads of physics and biology.
The project will probe and define the physical mechanisms of force transmission at the linker of nucleoskeleton and cytoskeleton (LINC) complexes.
These complexes are assemblies of proteins, which exhibit low elastic moduli on their own, but that collectively function as mechanotransducing hubs capable of conveying forces across the membrane of the nucleus, via mechanisms that remain poorly understood.
The goals are to identify the molecular tenants governing the formation, maintenance and disassembly of LINC protein clusters as a function of forces applied on the nucleus, to measure forces exerted at these clusters with fluorescent optical force sensors and to formulate physical models that define how LINC complex clustering participates to local changes in the shape of the nuclear membrane and force transmission.
The project will integrate theory and experiment.
It will be implemented through a multidisciplinary approach involving super-resolution microscopy, single molecule tracking, FRET imaging, cellular nanomanipulation, engineering of novel optical force sensors, their calibration using DNA origami nanoactuators, and theoretical modeling.
The project will lead to a better understanding of the mechanical properties of the nucleus, its membrane and cell mechanics in general.
This collaborative US/France project is supported by the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
Subawards are not planned for this award.
Cells receive many signals from their environment, including tensions and mechanical forces that are transferred all the way down to their nucleus.
Nuclear shape adaptations to those forces are critical for cell fate and function.
Yet, the physical and molecular principles underlying those adaptive mechanisms remain largely undefined.
By integrating state-of-the-art scientific approaches, this project will generate mechanistic understandings of nuclear mechanics and predictive insights into the organization of force-transmitting complexes in human cells.
The work will offer novel rationales to design bio-inspired and force-responsive nanodevices for human health.
It will also contribute new perspectives on the normal and defective mechanobiology of the nucleus, advancing our understanding of those critical cellular processes and the diseases that are caused by dysfunction in these systems.
A key aspect of the project is the training of early-career scientists, graduate students, undergraduates, and STEM-focused high school students to expose them to a unique research experience at the crossroads of physics and biology.
The project will probe and define the physical mechanisms of force transmission at the linker of nucleoskeleton and cytoskeleton (LINC) complexes.
These complexes are assemblies of proteins, which exhibit low elastic moduli on their own, but that collectively function as mechanotransducing hubs capable of conveying forces across the membrane of the nucleus, via mechanisms that remain poorly understood.
The goals are to identify the molecular tenants governing the formation, maintenance and disassembly of LINC protein clusters as a function of forces applied on the nucleus, to measure forces exerted at these clusters with fluorescent optical force sensors and to formulate physical models that define how LINC complex clustering participates to local changes in the shape of the nuclear membrane and force transmission.
The project will integrate theory and experiment.
It will be implemented through a multidisciplinary approach involving super-resolution microscopy, single molecule tracking, FRET imaging, cellular nanomanipulation, engineering of novel optical force sensors, their calibration using DNA origami nanoactuators, and theoretical modeling.
The project will lead to a better understanding of the mechanical properties of the nucleus, its membrane and cell mechanics in general.
This collaborative US/France project is supported by the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
Subawards are not planned for this award.
Funding Goals
THE GOAL OF THIS FUNDING OPPORTUNITY, "DIVISION OF PHYSICS: INVESTIGATOR-INITIATED RESEARCH PROJECTS", IS IDENTIFIED IN THE LINK: HTTPS://WWW.NSF.GOV/PUBLICATIONS/PUB_SUMM.JSP?ODS_KEY=NSF23615
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Los Angeles,
California
90089-2910
United States
Geographic Scope
Single Zip Code
Related Opportunity
University Of Southern California was awarded
Project Grant 2413064
worth $1,117,664
from the Division of Molecular and Cellular Biosciences in February 2025 with work to be completed primarily in Los Angeles California United States.
The grant
has a duration of 4 years and
was awarded through assistance program 47.074 Biological Sciences.
The Project Grant was awarded through grant opportunity Division of Physics: Investigator-Initiated Research Projects.
Status
(Ongoing)
Last Modified 2/20/25
Period of Performance
2/15/25
Start Date
1/31/29
End Date
Funding Split
$1.1M
Federal Obligation
$0.0
Non-Federal Obligation
$1.1M
Total Obligated
Activity Timeline
Additional Detail
Award ID FAIN
2413064
SAI Number
None
Award ID URI
SAI EXEMPT
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
490807 DIVISION OF MOLECULAR AND
Funding Office
490807 DIVISION OF MOLECULAR AND
Awardee UEI
G88KLJR3KYT5
Awardee CAGE
1B729
Performance District
CA-37
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
Modified: 2/20/25