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Mechanical Memory of Confined Migration

Award Number: R01GM160881
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: 09/04/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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Mechanical Memory of Confined Migration - Abstract: While metabolism has been recently therapeutically targeted as a mechanism to control proliferation, we now know that metabolism also plays an important role in cell migration. Our recent work has shown that the energetic state of a cell mediates its ability to migrate, its velocity, the path it will take, and the mode of migration it will employ. Interestingly, our recent work identified for the first time that migration through confined spaces primes cells to migrate faster and increase cellular ATP levels, behaviors that are maintained even after cells have left confinement. To our knowledge, this is the first evidence of cellular memory in response to confinement. Here, we propose to study the connection between confinement, migration, and cellular energetics with a focus on the effects of confinement on the mechanical memory of a cell. Using a microfabricated platform to control cell migration path and confinement, single cell biosensors of metabolic activity, molecular constructs to tune cell-matrix adhesion, and organoid models of wound healing, we will examine how cells develop metabolic and migration memory in confinement and we will describe the governing parameters of biomaterial architecture which harness this relationship to drive migration. In Aim 1, we will investigate the mechanism by which confinement confers migration and metabolic memory. In Aim 2, we will define the biomaterial parameter space that primes cells for migration, and we assay cell migration post-priming in vitro, ex vivo, and in vivo including in a human skin wound healing model. In Aim 3, we will take an orthogonal approach to studying the connection between metabolism and migration by sorting for the most energetic cells, disrupting metabolism using pharmacological agents, and testing for migration ability. Tuning migration and testing for energy while separately tuning energy and testing for migration will enable us to determine common drivers of each and determinants of cell priming for migration. The outcome of this work is the identification of a novel mechanism, that we have called mechanometabolic memory, by which biomaterial architecture primes cells for migration.


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: 2026 ( Subtotal = $393,665 )
2026	2026	WILLIAM MARSH RICE UNIVERSITY	6100 MAIN ST	HOUSTON	TX	77005	HARRIS	USA	Biomedical Research and Research Training	000	1	9/3/2026	NEW	$393,665
														Subtotal = $393,665

Grand Total All Awards = $393,665

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Mechanical Memory of Confined Migration

Award Number: R01GM160881

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: 09/04/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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