# Volumetric time-lapse imaging of biophysical cell-extracellular matrix interactions for systems mechanobiology research

> **NIH NIH R01** · CORNELL UNIVERSITY · 2022 · $398,011

## Abstract

Project Summary
The understanding of cancer has evolved rapidly over the last decade, particularly with discoveries regarding
the role of physical factors, such as extracellular matrix (ECM) stiffness and cellular forces, in carcinogenesis.
This research has shown that altered ECM stiffness is not just a symptom of tumors, but is now known to trigger
the actual onset of and progression of malignancy. Another key finding is that cellular traction stresses increase
with increasing metastatic potential, suggesting that cell traction forces could be a biomarker for the likelihood of
metastasis. Additionally, it has been found that (2D) collective behavior of cell populations can be significantly
different from that of isolated cancer cells, and that cell migratory behavior in 3D matrices is significantly different
migration on 2D surfaces. Although this has motivated the adoption of 3D microenvironments in cancer
mechanobiology research, current imaging methods to quantify ECM mechanical properties and local cellular
forces only provide 2D imaging, or when they do support 3D imaging, they do not provide long-range volumetric
measurements of collective mechanical behavior with cellular resolution. The central objective of this proposal
is to develop quantitative reconstruction capabilities for OCT-based techniques recently developed by the PI's
group for volumetric imaging of cell traction forces and ECM mechanical properties. These new quantitative
capabilities will be integrated with a fluorescence confocal microscopy module, to demonstrate a novel imaging
platform with unprecedented capabilities for time-lapse imaging studies of biophysical cell-ECM interactions in
3D environments. Aim 1 will develop the capabilities for quantitative 3D reconstruction of ECM mechanical
properties and validate it against rheometry and atomic force microscopy (AFM). Aim 2 will demonstrate our
OCT-based imaging of 3D cell traction forces using low-density cell cultures, integrating cellular resolution
imaging of ECM mechanical properties over millimeter-scale volumes. The demonstration of these novel,
integrated imaging capabilities in low-density cell cultures will be followed by a demonstration in dense tumor
spheroid cell cultures, where we will compare traction forces and ECM remodeling at the main spheroid boundary
versus surrounding invasion strands. Aim 3 will add a confocal fluorescence imaging module to our OCT system,
and we will demonstrate that this imaging platform can perform time-lapse reconstruction of 3D cell traction
forces and cell-induced changes in ECM mechanical properties in a multiple-cell population migrating in 3D
collagen. This will enable the first direct comparison of the time-varying traction forces of different cell types
simultaneously migrating in 3D collagen. Our novel 3D imaging platform for systems mechanobiology research
could lead to a deeper understanding of potential biophysical (mechanical) hallmarks of cancer, that can be used...

## Key facts

- **NIH application ID:** 10399569
- **Project number:** 5R01GM132823-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Steven Graham Adie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,011
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399569

## Citation

> US National Institutes of Health, RePORTER application 10399569, Volumetric time-lapse imaging of biophysical cell-extracellular matrix interactions for systems mechanobiology research (5R01GM132823-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399569. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*