# Imaging Molecular Level Details of Collagen Fibers by VSFG Microscopy

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $395,000

## Abstract

In this proposed project, we plan to fill the knowledge gap of the relationships between
microscopic self-assembled structures, collagen-molecule interactions and macroscopic fiber
morphologies of type-I collagen, the primary component of most human tissues and a commonly
used biomaterial for tissue engineering. By investigating collagen-water and collagen-protein
interactions in in vitro systems that mimic basic aspects of physiologically relevant three-
dimensional fibrillar tissue architectures, we aim to fill knowledge gaps in fundamental collagen
research. We will achieve this goal by developing a hyperspectral imaging technique – vibrational
sum frequency generation (VSFG) microscopy – at high repetition rates (400 kHz) and apply it to
collagen. The long-term vision is to develop new biophysics methods to reveal molecular-level
structures and interactions for pericellular space research and other complex biological
environments, and eventually applying it to study various pericellular environment related
diseases. In order to correlate spectral features to microscopic and macroscopic structures of
type I collagen, we plan to apply machine-learning techniques to analyze our data and extract
spectral signatures of collagen’s micro/macrostructures. We will two major scientific focuses: (A)
understanding molecular signatures of microscopic self-assembly fibrils structures and its
relationship to the macroscopic morphology (plan 1 and 2); and (B) investigating molecular level
collagen-molecule interactions (plan 3 and 4). Specific plans include:
 1. Obtaining hyperspectral VSFG images of collagen tissues to study their morphology in a
 label free and non-invasive manner
 2. Establishing molecular spectral signatures of self-assembled collagen fibril structures
 3. Understanding collagen-water interaction in first solvation layer of collagen fibers.
 4. Imaging spatial locations of chemicals and peptides that interact with collagens.
If successful, the significance is that a label free, vibrational mode specific imaging technique
specific for pericellular space will be available, which can reveal molecular level insights of
collagen structures and its interactions with surrounding molecules, pertinent to fibrosis and cell—
pericellular space interaction related diseases. This proposed project contributes to the scope of
NIGMS by developing new technology to reveal fundamental molecular-level principle,
mechanism and signatures related to morphology of collagen I at both micro- and macroscopic
scales, and collagen-molecule interactions, laying foundations for biophysical/biochemical
principles for future biomedical applications related to collagens.

## Key facts

- **NIH application ID:** 10697394
- **Project number:** 5R35GM138092-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Wei Xiong
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697394

## Citation

> US National Institutes of Health, RePORTER application 10697394, Imaging Molecular Level Details of Collagen Fibers by VSFG Microscopy (5R35GM138092-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10697394. Licensed CC0.

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