# Optical Control of Protein Activity in Live Cells by Plasmon Assisted Light Inactivation

> **NIH NIH R35** · UNIVERSITY OF TEXAS DALLAS · 2022 · $382,500

## Abstract

Abstract
Optical tools have unparalleled spatial and temporal precision and have been instrumental to better understand
various processes in modern medicine and biology. The overall goal of my research laboratory is to
understand the laser-plasmonic nanoparticle interactions and its effects at the interface between biological
systems and nanomaterials. Specifically, experimental techniques and methods have been developed to
understand the effects of nanoparticle plasmonic heating on proteins and lipids immediately next to the
nanoparticle. This has led to new enabling tools for optical protein manipulation and photosensitive
nanovesicles for molecular uncaging, as well as innovative diagnostic methods. This proposed research focus
on the development of optical control of protein activity in live cells, namely plasmon-assisted light inactivation
(PALI). PALI is based on pulsed laser heating (nanosecond) of plasmonic nanoparticles, and its thermally
confined heating to unfold and denature surrounding proteins within a few nanometers of nanoparticle surface.
Thus, PALI also effectively acts a unique nano temperature-jump (T-jump), an innovative experimental platform
to address a gap for protein unfolding investigations. In the next five years, I plan to develop my research
program in these two directions. Firstly, I will focus on developing this new optical tool to manipulate protein
activity in live cells with emphasis on G-protein coupled receptors (GPCR), an important and diverse class of
membrane receptors that mediate extracellular to intracellular signaling. This encompasses a systematic
approach to understand the interaction and trafficking of nanoparticles with GPCR, the cellular responses of
PALI on GPCR signaling, and finally the applicability of PALI on other GPCRs. I will primarily use a specific
GPCR, protease activated receptor 2 (PAR2) that is important for chronic pain, as a working model. To test for
other GPCRs, I will test GPCRs for neuropeptides, which are synergistic with our efforts to create neuropeptide
photosensitive nanovesicles. Secondly, I will concentrate on the characterization of the nano T-jump by
addressing two fundamental questions: (1) can the nanoparticle temperature be directly measured during
pulsed laser heating or after a short delay? (2) How does the protein unfold under nano T-jump? These
involves our existing collaborations with the Argonne National Lab to probe the gold lattice expansion using
advanced spectroscopy, and various structural and functional assays to measure the protein unfolding and
inactivation due to the nano T-jump. By the end of the five years, I anticipate solving important technical
challenges to demonstrate the use of PALI to manipulate protein activity in live cells through GPCRs, and
obtain a clear understanding of the temperature history and protein responses with the innovative nano T-jump
platform. These outcomes would generate interest to the broad research community and enable o...

## Key facts

- **NIH application ID:** 10476296
- **Project number:** 5R35GM133653-04
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Zhenpeng Qin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476296

## Citation

> US National Institutes of Health, RePORTER application 10476296, Optical Control of Protein Activity in Live Cells by Plasmon Assisted Light Inactivation (5R35GM133653-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10476296. Licensed CC0.

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