# Biomechanical Mechanisms Underlying Pathologic Hepatic Stellate Cell Behavior in Liver Fibrosis

> **NIH NIH F30** · NORTHWESTERN UNIVERSITY · 2022 · $42,301

## Abstract

PROJECT SUMMARY
The unregulated activation of hepatic stellate cells is a key step in the pathogenesis of liver fibrosis, a condition
which arises from multiple etiologies including viral infections, autoimmune diseases, metabolic disorders, and
toxic insults. When activated, stellate cells become myofibroblastic and adopt wound healing functions. Cirrhosis,
the most advanced stage of fibrosis, is associated with severe extrahepatic complications and a lifetime
increased risk for hepatocellular carcinoma. Fibrosis was once thought to be a unidirectional, irreversible
condition, but recent advances in curative treatment for hepatitis B and C have demonstrated that fibrosis is able
to regress. Therefore, effective antifibrotic therapies are in high demand to treat all stages of fibrosis from any
etiology. A promising approach is to inhibit the many functions of the activated stellate cell, or the activation
process itself, since these steps are central to driving disease pathogenesis.
Like all cells, activated stellate cells respond to cues delivered by their surrounding extracellular matrix (ECM).
Some of these cues are biochemical in nature. However, the mechanical properties of the ECM are also
instructive and provide signals that have profound effects on cell differentiation, migration, remodeling, and tissue
organization. The liver possesses two mechanical properties of notable interest: stiffness, the extent to which an
object resists deformation to an applied force, and stress relaxation, the ability to dissipate energy from an
applied force. An understanding of how stiffness and stress relaxation act independently and synergistically to
affect activated hepatic stellate cells may reveal previously unexplored opportunities for therapeutic
development. The objectives of the proposed research are therefore to modulate the behavior of hepatic stellate
cells by tuning matrix mechanical properties in a spatiotemporally precise manner. We have developed
photoresponsive poly(ethylene glycol)/liver ECM hybrid hydrogels with tunable stress relaxation that can be
reversibly stiffened with visible light. The Specific Aims of the proposed research are to (1) elucidate the
independent role of stress relaxation on hepatic stellate cell mechanical memory and (2) assess hepatic stellate
cell durotactic migratory capacity as a function of stress relaxation. In addition to functional readouts of healthy
and diseased cell phenotypes, we will use established metrics for cellular mechanosensing, such as YAP nuclear
translocation, to develop clear structure-function relationships between ECM mechanics, mechanosensing, and
cell behavior. The anticipated product of this research is a causal understanding of the response of stellate cells
to mechanical signals. This research will be a collaborative effort between Northwestern University’s Department
of Chemistry, Northwestern Memorial Hospital, and external collaborators. In carrying out the proposed Aims
and associ...

## Key facts

- **NIH application ID:** 10538260
- **Project number:** 1F30DK129002-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Vivian Zhang
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,301
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538260

## Citation

> US National Institutes of Health, RePORTER application 10538260, Biomechanical Mechanisms Underlying Pathologic Hepatic Stellate Cell Behavior in Liver Fibrosis (1F30DK129002-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10538260. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*