# Super-resolution imaging of protein dynamics in the extracellular matrix

> **NIH NIH R35** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $353,698

## Abstract

Project Summary
We seek to understand how the physiochemical environment of the extracellular matrix affects the diffusion,
structure, and folding of proteins. The extracellular matrix is spatially heterogeneous at nanoscales and can
change over time. But current imaging methods are limited in spatial and temporal resolutions, while biochemical
techniques are designed for model, pristine solutions that differ from the complexity of the extracellular matrix.
Therefore, how proteins function locally in the extracellular matrix is an underexplored area in biophysics. We
propose to understand how proteins function and interact in the complex extracellular matrix environment, and
how the nanoscale variation in the chemical and physical composition of this environment can locally change
protein dynamics. To achieve this, we will use a correlation-based super-resolution microscopy developed by
our lab that can access the time- and spatial-scales of protein dynamics within the extracellular matrix. The goals
of this proposal are to: 1) identify how the nanoscale chemical and steric properties of the extracellular matrix
control protein diffusion, structure, and folding; 2) determine how cells tune the dynamics of proteins by
changing the extracellular matrix; 3) develop instrumental and analysis methods that access the spatiotemporal
regimes required to understand protein function in the extracellular environment. Achieving our goals will reveal
the extracellular matrix and protein dynamics that drive biological regulation and will provide researchers with
methods to understand and potentially control extracellular delivery of signaling proteins or therapeutics. Overall,
an entirely new area of biology – the extracellular matrix - will be explored by super-resolution microscopy; the
findings can be broadly applied to other biomolecules, cells, and tissues of relevance to fundamental biophysics,
drug-delivery/therapeutics, and disease.

## Key facts

- **NIH application ID:** 10271827
- **Project number:** 1R35GM142466-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Lydia Kisley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $353,698
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271827

## Citation

> US National Institutes of Health, RePORTER application 10271827, Super-resolution imaging of protein dynamics in the extracellular matrix (1R35GM142466-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10271827. Licensed CC0.

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