Fibrosis and remodeling of extracellular matrix (ECM) are involved in many diseases affecting health, such as tumors, wound healing, and chronic inflammation. During fibrosis, tissues undergo changes in their viscoelastic properties, i.e., how they resist deformation like a solid and dissipate stress over time like a fluid. Independent of stiffness, an applied stress relaxes rapidly in a more viscous, liquid-like matrix, whereas in a more elastic, solid-like material, stress relaxes slowly (Vining and Mooney, 2017). The Vining Lab investigates the impact of viscoelasticity on inflammation in fibrotic tissues and develops new immunotherapies in cancer.
- We utilize an artificial ECM to dissect a mechanical checkpoint of monocyte fate and develop strategies to target myeloid inflammation in vivo. Monocytes are a type of white blood cells that impact the local immune response by producing cytokines and differentiating into phagocytic and antigen-presenting cells, like macrophages and dendritic cells.
- We first investigated this concept in hematopoietic malignancies that result in myelofibrosis (Vining, K.H., et al., Nature Materials, 2022). The data revealed changes of viscoelasticity in diseases associated with myelofibrosis, more than changes in stiffness alone, regulates inflammation and differentiation of monocytes, and is targetable by a PI3K-gamma inhibitor.
- This work has potential broad applications in fibrotic and inflammatory diseases.
Vining, K.H., Mooney, D.J. (2017). Mechanical forces direct stem cell behavior in development and regeneration. Nature Reviews Molecular Cell Biology 18, 728-742. PMCID: PMC5803560
Vining, K.H.*, Marneth, A.*, Adu-Berchie, K., et al. A mechanical checkpoint regulates monocyte differentiation in fibrotic niches. Nature Materials, July 2022. https://doi.org/10.1038/s41563-022-01293-3. *Authors contributed equally.
