arXiv subjects

Harikrishnan Parameswaran

Publications and source records attributed to Harikrishnan Parameswaran.

2 recordsLinked to original sources

arXiv2026

Local intercellular coupling is sufficient for long-range calcium signaling

Long-range intercellular calcium (Ca2+) signaling coordinates biological processes ranging from fertilization to contraction and cell death. The classical model attributes this long-range propagation to rapid diffusion of inositol 1,4,5-trisphosphate (IP3) through gap junctions. However, recent evidence that IP3 diffuses far more slowly than previously believed, and that Ca2+ oscillations persist even when gap junctions are disassembled, indicates that an alternative mechanism must sustain long-range communication. Here we develop a computational model showing that local coupling between neighboring cells is sufficient to generate and propagate regenerative Ca2+ oscillations across a cell population without fast molecular diffusion. Each cell is treated as an oscillator whose intrinsic frequency is set by its local IP3 concentration through an IP3-dependent refractory period, and neighboring cells are coupled using a Kuramoto nearest-neighbor framework. In a dual-stiffness regime, cells on a stiff extracellular matrix entrain their soft-matrix neighbors, producing an offset traveling wave of Ca2+ release. This reproduces the finite spatial range of influence (~8 cell lengths) observed experimentally. Our findings propose a diffusion-independent paradigm for calcium signaling in which local intercellular coupling drives long-range communication, offering insight into how localized ECM stiffening in asthma and fibrosis may produce systemic effects.

q-bio.CB↗

arXiv2025

Intercellular contact is sufficient to drive Fibroblast to Myofibroblast transitions

Fibroblast cells play a key role in maintaining the extracellular matrix. During wound healing, fibroblasts differentiate into highly contractile myofibroblasts, which secrete extracellular matrix proteins like collagen to facilitate tissue repair. Under normal conditions, myofibroblasts undergo programmed cell death after healing to prevent excessive scar formation. However, in diseases like fibrosis, the myofibroblasts remain active even after the wound is closed, resulting in excessive collagen buildup and a stiff, fibrotic matrix. The reasons for the persistence of myofibroblasts in fibrosis are not well understood. Here, we show the existence of a mechanism where direct physical contact between a fibroblast and a myofibroblast is sufficient for fibroblasts to transition into myofibroblasts. We demonstrate that the fibroblast-myofibroblast transition can occur even in the absence of known biochemical cues, such as growth factor activation or mechanical cues from a stiff, fibrotic matrix. Furthermore, we demonstrate that contact-based fibroblast-myofibroblast activation can be inhibited by the G{\alpha}q/11/14 inhibitor FR900359, which prevents the formation of myofibroblasts. These findings provide new insights into the persistence of fibrosis despite therapeutic interventions, suggesting a potential strategy for targeting the fibroblast-to-myofibroblast transition in fibrotic conditions.

q-bio.CB↗