# Using graphene to probe the role of membrane cholesterol in stem cell proliferation and differentiation

> **NIH NIH R21** · FLORIDA ATLANTIC UNIVERSITY · 2020 · $186,875

## Abstract

Summary
The rapid advances in stem cell technology have offered the hope for neurodegenerative diseases like
Alzheimer’s disease and Parkinson’s disease. Transgene- or chemical-assisted dedifferentiation and
transdifferentiation of somatic cells produce versatile neuronal stem cells or precursor cells, which can be further
differentiated to neurons. However, getting mature neurons and functional synapses remains to be a lengthy and
inefficient process, especially for dopaminergic neurons. New evidence showed the vital influence of extracellular
microenvironment in neurodevelopment and synaptogenesis.
Cholesterol is a unique and essential lipid in the eukaryotic plasma membrane. In addition to its biophysical role
in membrane organization, cholesterol also actively regulates transmembrane proteins including cytokine
receptors and adhesion proteins by direct binding or promoting lipid rafts. Hence, it plays an important role in
regulating neuronal stem cells. In fact, ample evidence has shown that membrane cholesterol is required in
neuronal differentiation, neurite growth, synaptogenesis and plasticity. However, there are few tools including
statins, cyclodextrins and genetic mutations (e.g. NPC1) to reduce cholesterol. Notably, they either cause cell-
wide cholesterol shortage or nonspecifically reduce other steroid lipids. More limited is the way to actively
increase cholesterol, which is only possible via cyclodextrin-cholesterol complex. This is particularly problematic
for neurons or neuronal precursor cells since they already have the highest membrane cholesterol concentration
than almost all other types of cells in the human body.
Recently, we have discovered that graphene, a novel carbon nanomaterial, selectively interacts with and
enriches cholesterol in the plasma membrane of various cell types including neurons. By so doing, graphene
potentiates synaptic transmission and receptor activity in a cholesterol-dependent manner. Consistently, it was
reported by several groups that graphene promoted neural stem cell proliferation and differentiation with little
toxicity. Therefore, we propose to study how graphene can be used to manipulate membrane cholesterol and to
promote neuronal differentiation as well as synaptic maturation. First, we will further study molecular mechanism
underlying graphene’s interaction with membrane cholesterol and its contribution to membrane organization.
Second, we will test graphene’s effect on promoting neurogenesis and maturation from stem cells. Third, we will
explore the potential use of graphene nanoflakes to selectively enhance synaptogenesis and dopamine release
in stem-cell derived dopaminergic neurons. By so doing, we hope to illustrate a practical path of utilizing
graphene in neuronal stem cell research and neuroregeneration, especially in the context of treating currently
incurable neurodegenerative diseases like Parkinson’s disease.

## Key facts

- **NIH application ID:** 9983544
- **Project number:** 5R21AG061656-02
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** Qi Zhang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,875
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983544

## Citation

> US National Institutes of Health, RePORTER application 9983544, Using graphene to probe the role of membrane cholesterol in stem cell proliferation and differentiation (5R21AG061656-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983544. Licensed CC0.

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