{"id":4550,"date":"2025-12-11T19:35:32","date_gmt":"2025-12-12T00:35:32","guid":{"rendered":"https:\/\/www.bu.edu\/mechanobiology\/?page_id=4550"},"modified":"2025-12-11T19:35:32","modified_gmt":"2025-12-12T00:35:32","slug":"poster-presentation-vasuretha-chandar","status":"publish","type":"page","link":"https:\/\/www.bu.edu\/mechanobiology\/poster-presentation-vasuretha-chandar\/","title":{"rendered":"Poster Presentation: Vasuretha Chandar"},"content":{"rendered":"

ABSTRACT<\/strong><\/p>\n

Intercellular Contact Is Sufficient To Drive Fibroblast-to-Myofibroblast Transitions <\/b><\/b><\/p>\n

Vasuretha Chandar1<\/span>, Benjamin M. Goykadosh1<\/span>, Harikrishnan Parameswaran1 <\/span><\/p>\n

1<\/span>Department of Bioengineering, Northeastern University, Boston, MA, 02115<\/p>\n

Introduction: <\/b>Fibroblasts are essential for maintaining the extracellular matrix and facilitate wound repair by transitioning into contractile myofibroblasts1<\/span>. Under normal conditions myofibroblasts secrete collagen and undergo programmed cell death after healing to prevent excessive scarring2,3 <\/span>. However, in progressive age-related lung diseases like Idiopathic Pulmonary Fibrosis (IPF), persistent myofibroblast activation drives collagen accumulation and matrix stiffening4<\/span>. IPF incidence rises with advancing age, with most diagnoses occurring between 65-70 years5<\/span>. Despite therapies targeting matrix stiffness and canonical biochemical pathways, IPF continues to progress rapidly without cure, with a median survival rate of only 3-5 years post diagnosis6<\/span>. Clearly, alternative mechanisms functioning independently of the known biochemical or stiff matrix cues contribute to fibrosis.<\/p>\n

Results: <\/b>In our work, we identify a previously unrecognized mechanobiological pathway in which direct physical contact between fibroblasts and myofibroblasts is sufficient to trigger fibroblast-to-myofibroblast transition (FMT), even in the absence of a stiff matrix or exogenous signaling factors. We show that contractility (Mii<\/span>) in fibroblasts rises significantly upon contact with a myofibroblast, precedes phenotype change and mechanically activates Phospholipase C, driving the transition. This contact mediated activation is blocked by the G\u03b1q inhibitor (FR900359). Strikingly, TGF\u03b2 inhibitors also act on myofibroblasts in soft matrices (0.3kPa) by rapidly reducing cytoskeletal tension, underscoring tension as a central regulator of FMT.<\/p>\n

Conclusion: <\/b>These findings broaden the understanding of fibrosis by demonstrating that myofibroblast activation can occur through cell-cell interactions and intrinsic mechanotransduction, not only through external mechanical or biochemical cues. Our work highlights GqGPCR signaling as a critical mediator and cytoskeletal tension as a unifying mechano-therapeutic target and opens new avenues for interventions aimed at halting fibrosis progression.<\/p>\n

Methods: <\/b>Fibroblast and myofibroblast populations were generated by leveraging cellular mechanical memory through culture on soft and stiff substrates, respectively. Traction force and monolayer stress microscopy were used to quantify changes in cytoskeletal tension. Fluorescently tagged Calcium and PIP2 indicators were employed to assess signaling dynamics. YAP and \u03b1-SMA immunostaining were used to evaluate fibroblast-to-myofibroblast phenotype transitions.<\/p>\n

<\/span>References: <\/b><\/b><\/p>\n

1. Desmouliere, A., Darby, I. A., Laverdet, B. & Bont\u00e9, F. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol <\/i>301 (2014) doi:10.2147\/CCID.S50046.<\/p>\n

2. Hinz, B. The role of myofibroblasts in wound healing. Curr Res Transl Med <\/i>64, 171\u2013177 (2016).<\/p>\n

3. Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C. & Brown, R. A. Myofibroblasts and mechano: Regulation of connective tissue remodelling. Nature Reviews Molecular Cell Biology <\/i>vol. 3 349\u2013363 Preprint at https:\/\/doi.org\/10.1038\/nrm809 <\/span>(2002).<\/p>\n

4. Martinez, F. J. et al. <\/i>Idiopathic pulmonary fibrosis. Nat Rev Dis Primers <\/i>3, 17074 (2017).<\/p>\n

5. Pergolizzi, J. V et al. <\/i>What Do We Need to Know About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative Review and Update. Adv Ther <\/i>40, 1334\u20131346 (2023).<\/p>\n

6. Golchin, N. et al. <\/i>Incidence and prevalence of idiopathic pulmonary fibrosis: a systematic literature review and meta-analysis. BMC Pulm Med <\/i>25, 378 (2025).<\/p>\n","protected":false},"excerpt":{"rendered":"

ABSTRACT Intercellular Contact Is Sufficient To Drive Fibroblast-to-Myofibroblast Transitions Vasuretha Chandar1, Benjamin M. Goykadosh1, Harikrishnan Parameswaran1 1Department of Bioengineering, Northeastern University, Boston, MA, 02115 Introduction: Fibroblasts are essential for maintaining the extracellular matrix and facilitate wound repair by transitioning into contractile myofibroblasts1. Under normal conditions myofibroblasts secrete collagen and undergo programmed cell death after healing […]<\/p>\n","protected":false},"author":14358,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages\/4550"}],"collection":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/users\/14358"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/comments?post=4550"}],"version-history":[{"count":1,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages\/4550\/revisions"}],"predecessor-version":[{"id":4552,"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/pages\/4550\/revisions\/4552"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/mechanobiology\/wp-json\/wp\/v2\/media?parent=4550"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}