# Nanoscale probes for sensing molecular functions in live cells

> **NIH NIH R35** · STANFORD UNIVERSITY · 2021 · $814,478

## Abstract

Project Summary / Abstract:
 This MIRA proposal merges two distinct projects supported by R01GM128142, “The role of membrane
curvature in surface nanotopography-induced cell functions”, and R01GM125737, “Developing nanoscale
electrophysiology sensors for robust intracellular recording”. While the two projects focus on different biological
questions, the unifying theme is to develop nanoscale probes to elucidate the cellular machinery in the intricate
environment of living cells. In this proposal, we discuss topics along the lines of the parent grants, focusing on
the significance of the biological problems, our recent and evolving results, and directions for the future. For
the first project, the long-term goal is to understand how membrane curvature regulates biochemical signals
that are transmitted through the cell-matrix interface. At the cell-matrix interface, where the cells make physical
contact with extracellular matrices, the membrane may be locally deformed by matrix topography or
mechanical forces. As it remains a challenge to manipulate nanoscale membrane curvature in live cells, our
current understanding of how local membrane curvature affects signal transmission is limited. We propose to
use nanotechnology-based precision engineering to control interface membrane curvature in live cells. We
seek to understand how cellular processes are affected by membrane curvature and the underlying molecular
mechanisms. The knowledge gained will help us understanding how cells interact with extracellular matrix and
also help us designing biomaterials for better integration with cells. For the second project, we are developing
vertical nanoelectrodes into a robust and easy-to-use electrophysiology tool that can reliably achieve parallel
intracellular recording of cardiomyocytes with minimal perturbation. Simultaneous nanoelectrode and patch
clamp recordings on same cells confirmed that nanoelectrodes accurately record action potential waveforms
for classification and characterization of stem-cell-derived cardiomyocytes. These nanoelectrodes will enable
us to understand how in vitro interventions accelerate the maturation of stem-cell-derived cardiomyocyte.
Furthermore, nanoelectrodes provide an ideal tool for monitoring the generation and resealing of membrane
pores on cardiomyocytes that are prone to membrane rupture due to their large size and strong mechanical
contraction. We will use nanoelectrode to investigate how proteins participate in the membrane resealing
process. We hope to achieve a broad impact by combining the development of new tools with applications to
specific biological systems.

## Key facts

- **NIH application ID:** 10201347
- **Project number:** 1R35GM141598-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Bianxiao Cui
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $814,478
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201347

## Citation

> US National Institutes of Health, RePORTER application 10201347, Nanoscale probes for sensing molecular functions in live cells (1R35GM141598-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201347. Licensed CC0.

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