# Understanding the viscoelasticity, surface tension, and membrane interactions of biomolecular condensates in live cells

> **NIH NIH R35** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $217,374

## Abstract

PROJECT SUMMARY
Phase separation in cells can lead to the formation of biomolecular condensates, also known as membraneless
organelles. The material properties of these condensates are associated with various biological and pathological
roles. For example, the surface tension of a liquid condensate governs its interaction with both membranous and
membraneless organelles, regulating processes such as autophagy, vesicle trafficking, nucleoli organization,
microtubule branching, P granule growth, and cell surface signaling. Under abnormal conditions, several types
of biomolecular condensates change from liquid states to solid fibrils that resemble the hallmarks of
neurodegeneration. However, current understanding of the material properties of biomolecular condensates
severely lacks in two important aspects: 1) quantitative assessments of condensates in live cells; 2) a
mechanistic understanding of factors that control the properties and functions of condensates.
 Recently, we demonstrated the use of micropipette aspiration, a technique known for studying membranes,
in quantifying both the surface tension and viscosity of protein condensates, free from common sources of
artifacts. Importantly, our technique shares a large part of its core hardware with patch-clamp, a well-established
tool used by neuroscientists to record electrical signals in live cells and animals. In ongoing experiments, we
have applied the technique to several different types of biomolecular condensates. This includes proteins
associated with neurodegeneration as well as synapsin, a highly abundant neuronal protein that regulates
synaptic vesicle clustering and transmission. Furthermore, we have tested the compatibility of our technique with
cellular patch-clamp recording. Based on these preliminary data, we hypothesize that micropipettes can be
broadly applied to understand the material properties of biomolecular condensates in live cells.
 In the next five years, we will first develop the micropipette-based technique into an accurate, broadly
applicable, and easily accessible tool for quantifications of biomolecular condensates in common cell lines and
primary neurons. This new tool will allow us to collect the much-needed quantitative data that can give direct
insights into the roles of condensate material properties in mediating a wide range of biological processes. We
will study the role of surface tension in governing the integrity of synapsin condensates, and the role of
condensate viscosity in modulating the dynamics of synaptic vesicle release and exocytosis. We will also
investigate the interplays between cell membrane mechanics and membrane-wetting condensates such as those
at synapses and tight junctions. On the front of pathological relevance, we will focus on elucidating condensate
material properties that underlie the aberrant phase transition of neurodegeneration-associated proteins. We will
take advantage of the cytosolic access of our technique to directly test ...

## Key facts

- **NIH application ID:** 10499504
- **Project number:** 1R35GM147027-01
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Zheng Shi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $217,374
- **Award type:** 1
- **Project period:** 2022-09-21 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499504

## Citation

> US National Institutes of Health, RePORTER application 10499504, Understanding the viscoelasticity, surface tension, and membrane interactions of biomolecular condensates in live cells (1R35GM147027-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499504. Licensed CC0.

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