# THREE-DIMENSIONAL MECHANO-MICROSCOPY OF THE STEM CELL NICHE

> **NIH NIH R21** · CORNELL UNIVERSITY · 2020 · $191,422

## Abstract

Biophysical properties of cellular microenvironments can act to direct the self-renewal and differentiation fate
outcomes of stem cells in multiple tissue types. As an example, the stem cells resident in skeletal muscles
(MuSCs, also called satellite cells) are highly sensitive to elasticity of their surrounding “niche” microenvironment.
In culture models, elastic substrates corresponding to the more stiff microenvironments observed in muscle aging
and diseases such as muscular dystrophy can induce MuSCs to differentiate instead of self-renew, which is a
hallmark of muscle dysfunction in these pathological settings. Characterization of the viscoelastic properties of
endogeneous stem cell niches within intact 3D tissues ex vivo or in vivo would provide critical insights into the
consequence of microenvironmental mechanical changes on stem cell fate outcomes, but is not possible with
current rheology and imaging approaches. Thus, new imaging methods are needed to achieve 3D mapping of
local mechanical properties in and around individual anatomically-defined stem cell niches with cellular resolution
and capable of non-destructive longitudinal assessment. The central objective of this proposal is to demonstrate
photonic force optical coherence elastography (PF-OCE) for volumetric imaging of the mechanical properties of
individual stem cell microenvironments in intact tissue explants and engineered biomaterial niches. PF-OCE will
perform mechanical loading (`palpation') using photonic radiation pressure, combined with ultra-precise phase-
sensitive optical coherence tomography (OCT), to detect the resulting displacements. Our approach differs from
conventional laser tweezers-based active microrheology that uses optical gradient forces to generate transverse
bead oscillations, and instead, PF-OCE utilizes low-NA on-axis radiation-pressure forces, which is a key factor
enabling large-scale volumetric interrogation. We will apply PF-OCE to a muscle stem cell system, evaluating
both biomimetic hydrogel culture substrates, previously developed by the Co-Investigator to mimic the
viscoelastic properties of skeletal muscle tissue, and in muscle myofiber explant tissue, which maintains key
molecular and mechanical aspects of the muscle stem cell niches in short-term culture. Specific Aim 1 will
develop PF-OCE for quantitative reconstruction of viscoelastic properties of homogeneous muscle-mimetic
poly(ethylene glycol) hydrogels, and demonstrate the ability to distinguish between photonic force (mechanical)
and photothermal (heating) responses. Shear rheometry will be used to validate PF-OCE reconstructions of
shear storage and loss moduli. Specific Aim 2 will apply PF-OCE to image the viscoelastic properties of individual
muscle stem cell niches in intact muscle fiber explants and correlate them with stem cell fate outcomes. Stem
cell fates, tracked via time-lapse two-photon microscopy, will be co-registered with 3D volumetric mechano-maps
throughout myofiber...

## Key facts

- **NIH application ID:** 9851395
- **Project number:** 5R21EB024747-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Steven Graham Adie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,422
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851395

## Citation

> US National Institutes of Health, RePORTER application 9851395, THREE-DIMENSIONAL MECHANO-MICROSCOPY OF THE STEM CELL NICHE (5R21EB024747-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851395. Licensed CC0.

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