# Cellular regulation of viscosity

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $308,306

## Abstract

Viscosity is fundamental to biochemical reactions and hence, life itself. Temperature affects the
diffusion rate of molecules and in turn modulates the rate of reactions in non-living systems. For decades it has
been assumed that cells in living organisms are subject to the same principles that connect temperature,
viscosity, diffusion and reaction rates. Yet it has been a mystery how the incredibly complex diffusion-based
interaction networks of a cell are robust to these fluctuations, since perturbation of reaction kinetics in even one
pathway has the potential to impact multiple aspects of cellular functioning. The regulation of intracellular
viscosity as a strategy to mitigate changes in diffusion due to the environment has been largely
unexplored. This proposal addresses how intracellular viscosity is actively regulated, the effects of
viscosity on cellular processes, and viscosity dysregulation in disease.
 We recently discovered that cytosolic diffusion rates and viscosity-controlled reaction rates are held
invariant across at least 20° C of steady state temperatures in Saccharomyces cerevisiae. We found that
cellular viscosity temporarily increases in response to acute stress. We named this phenomenon
“viscoadaptation”. Viscoadaptation is both a homeostatic mechanism for maintaining constant viscosity
despite fluctuations in temperature as well as an acute response to a variety of environmental stressors.
Viscoadaptation acts via production of the viscous carbohydrate glycogen that is linked to human health and
disease, and we hypothesize that low energy levels trigger viscoadaptation.
 The discovery of viscoadaptation marks a major advance in our understanding of how cells regulate
their biophysical properties. Yet many mysteries remain, including 1) how viscodaptation affects the biophysical
properties of cells, 2) what signaling pathways regulate viscoadaptation. We propose to (aim 1) study the
effect of glycogen on protein mobility and structure (aim 2) investigate how the pathways regulating
viscosity in yeast and human cells.
 The proposed studies will examine regulation of a fundamental yet largely unexplored biophysical
feature of cells, viscosity. This will elucidate the long overlooked contribution of viscosity to critical cellular
processes and the mechanisms by which this fundamental property is actively regulated in cells. In doing so,
this work has the potential to reframe disease conditions from the perspective of viscosity dysregulation and
usher in a new conceptual framework of "viscosity-related" pathologies.

## Key facts

- **NIH application ID:** 10564013
- **Project number:** 1R01GM148526-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Onn Brandman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $308,306
- **Award type:** 1
- **Project period:** 2023-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10564013

## Citation

> US National Institutes of Health, RePORTER application 10564013, Cellular regulation of viscosity (1R01GM148526-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10564013. Licensed CC0.

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