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Advanced label-free microscopy to link cell structure to mechanobiology.

Award Number: R35GM165570
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: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Advanced label-free microscopy to link cell structure to mechanobiology. - Project Summary Mechanobiology plays a critical role in the development and function of living systems and in the progression of disease. The cytoskeleton, the fundamental structure mediating force transmission, is also a common target of therapeutics. Studying how changes in the structure of the cell lead to emergent properties like viscoelasticity is key to understanding fundamental biology and for developing new therapies. Currently, visualization of the cytoskeleton requires exogenous dyes which can damage the underlying protein network, and which are also subject to photobleaching, preventing long-term studies. Measurements of cell mechanical properties, similarly, require probing and stretching of the cell, perturbing its structure. Linking cytoskeletal structure to a cell’s emergent mechanical properties in live, untouched, and unlabeled cells is therefore challenging. This work proposes to develop new cellular imaging tools and methods for understanding how cell structure contributes to mechanobiology. Quantitative phase imaging (QPI) and specifically, holotomography (HT) will be explored as a label-free, nondestructive, non-contact, and quantitative method of visualizing cytoskeletal structure and predicting cell viscoelasticity. HT is an emerging optical imaging platform which creates three-dimensional protein mass density maps of cells with ~200 nm resolution. However, it is currently unclear how these tomograms correlate with cyto-mechanical structure or emergent properties like viscoelasticity. The focus of this effort will be to link HT tomograms with cytoskeletal structure and viscoelasticity, removing the requirement to fluorescently label the cell to measure its structure, or mechanically probe the cell to measure its mechanics. Using a unique holotomography system with integrated spinning disk confocal microscope, covariance between HT volumes and specific structures within the cytoskeleton (actin, tubulin) will be explored to determine whether HT can predict cytoskeleton organization without labels. Incorporation of Brillouin microscopy will add mechanical specificity to HT, while the addition of Raman spectroscopy will add chemical specificity. We will use the tools developed by this effort to assess the effects of cytoskeletal and macromolecular order on cell viscoelasticity, and apply these tools to measure the cytostructural and mechanobiological impacts of various actin and tubulin-targeting drugs longitudinally and label- free. This work both addresses structure-function relationships in fundamental biology while developing innovative technologies to enable discoveries in biomedical research.


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 = $394,917 )
2026	2026	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	1	7/14/2026	NEW	$394,917
														Subtotal = $394,917

Grand Total All Awards = $394,917

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Advanced label-free microscopy to link cell structure to mechanobiology.

Award Number: R35GM165570

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: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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