# Protein assemblies as genetically encoded mechanical actuators for intracellular mechanobiology research

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $409,375

## Abstract

Title: Protein assemblies as genetically encoded mechanical actuators for intracellular
mechanobiology research
Project Summary
Cells are continuously subjected to mechanical cues that regulate diverse biochemical and biophysical
processes. In the rapidly growing field of mechanobiology, various methods, including but not limited to
substrate engineering, optical/magnetic tweezers, atomic force microscopy, pipette aspiration, and
microfluidics, have been developed and exploited for mechanical manipulation of live cells. Though with
grand success, these paradigms primarily apply mechanical forces at the cellular surface, while direct
intracellular perturbation remains underexplored. The limited capability of intracellular force exertion
impedes in-depth investigation of critical fundamental questions such as how forces are translated inside
the cells and regulate the output functions. Therefore, we plan to fill the technological gap by developing
a toolbox of genetically encoded peptides/proteins as intracellular mechanical actuators. We will rationally
design and engineer peptides/proteins that can spontaneously form in-cellulo nanoscopic or microscopic
assemblies with various sizes, shapes, surface chemistries, and mechanical properties to mimic
intracellular mechanical milieu. The corresponding biological responses of cells will be probed by
molecular sensors and optical microscopy. With the assistance of numerical simulation, the mechanical
interactions between protein assemblies and subcellular structures will be recapitulated and correlated
to the change of biological processes. The tools, once developed, will be exploited to study
mechanoresponses of membrane receptors and cell nuclei. The genetically encoded mechanical
actuators can afford several distinct advantages: 1) It allows direct, chronic, and precise exertion of force
intracellularly; 2) A large number of cells can be transformed and characterized simultaneously, enabling
high-throughput probing and analysis; 3) The genetic delivery of the tool and the contact-free perturbation
makes it readily applicable to more complex and physiologically relevant biological systems, such as
organoids, ex-vivo tissues, and even the live animal models. We believe the new genetically encodable
tools can shift the paradigm for intracellular mechanobiology research and help advance our
understanding of organelle mechanosensing,

## Key facts

- **NIH application ID:** 10909246
- **Project number:** 5R35GM147274-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Dingchang Lin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909246

## Citation

> US National Institutes of Health, RePORTER application 10909246, Protein assemblies as genetically encoded mechanical actuators for intracellular mechanobiology research (5R35GM147274-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909246. Licensed CC0.

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