Biology subjects

Emon, B.

Publications and source records attributed to Emon, B..

5 recordsLinked to original sources

bioRxiv2026

CAF contractility controls collagen stiffness through history-dependent competition between mechanical and proteolytic remodeling

Mechanical remodeling by cancer-associated fibroblasts (CAFs) stiffens tumors and can restrict molecular transport, yet the time-resolved coupling between cellular force and matrix mechanical state is poorly defined. Here we use a microfabricated force sensor integrated with 3D CAF-collagen tissue to measure CAF-generated force and collagen stiffness continuously during pharmacological perturbation. ROCK or non-muscle myosin II inhibition reduced force and remarkably drove collagen stiffness below its initial value rather than merely arresting stiffening. This softening was prevented by broad-spectrum MMP inhibition, but only modestly altered by lysyl oxidase inhibition, supporting a competition between force-driven collagen compaction and proteolytic remodeling. Second-harmonic generation imaging showed shorter, thinner and less aligned fibers after ROCK inhibition, while fluorescence recovery after photobleaching indicated faster dextran transport. Moreover, CAF contractile adaptation depended strongly on the duration of inhibition, with reversible recovery after brief treatment, a hyper-contractile rebound following prolonged treatment and washout, and partial force recovery during continuous exposure. These findings identify CAF-matrix mechanics as a dynamic, treatment-history-dependent balance and provide a framework for designing stromal interventions that alter stiffness and transport.

bioengineering↗

bioRxiv2026

Exercise engages a mechanically activated astrocyte state linking muscle activity to hippocampal plasticity

Physical exercise promotes brain health in part through muscle-derived factors that enter the brain, but how peripheral signals are translated into neural responses remain unclear. Here, we identify astrocyte contraction as a previously unrecognized physiological response to exercise signals that may contribute to adult hippocampal neurogenesis. In vivo, voluntary running rapidly induced nuclear localization of the mechanically sensitive transcriptional regulator Yes-associated protein (YAP), and increased non-muscle myosin II phosphorylation in hilar astrocytes in mice, consistent with acute contraction. Using an in vitro platform with ultrasensitive force sensors, we found that factors released by contracting skeletal muscles activated astrocytes which in turn increased contraction that was necessary and sufficient for their proliferation and expansion. Activated astrocytes subsequently released soluble factors that modulated neuronal network tension and promoted immature neuron abundance. These findings identify astrocyte contractility as a physiological transducer of exercise-derived muscle signals and establish cellular force generation as a potential mechanism regulating neuroplasticity.

neuroscience↗

bioRxiv2025

Biomechanical 3D tumor models on a micro-milled high-throughput force sensor array

The tumor microenvironment plays a critical role in drug resistance, with extracellular matrix (ECM) mechanics, cell-cell crosstalk, and transport barriers contributing to poor therapeutic outcomes. Traditional two-dimensional (2D) cultures fail to capture these features, and drug efficacy in 2D often does not translate to three-dimensional (3D) models or in vivo tumors. Here, we introduce a 3D tumor model integrated with a high- throughput biomechanical sensor array that enables simultaneous measurement of cellular forces, matrix remodeling, and molecular transport. Fabricated using a scalable and cost-effective micro-milling approach, the platform allows parallel generation of multiple tumor constructs within a single dish. Using patient-derived pancreatic ductal adenocarcinoma (PDA) cells and stromal fibroblasts, we show that responses to gemcitabine and all-trans retinoic acid (ATRA) in 3D differ markedly from 2D cultures, consistent with clinical observations. By integrating biochemical and biomechanical readouts, this technology provides a more physiologically relevant tumor model and a powerful tool for preclinical drug testing and personalized medicine.

cancer biology↗

bioRxiv2024

A fast, muscle-actuated biohybrid swimming robot

The integration of biological actuators with soft scaffolds has led to biohybrid robots including microscale flagellate-like swimmers which generate thrust by waving their flagella-like tails. However, they achieve swimming speeds of only 0.014 body lengths per minute, Reynolds number (Re) [~] 10-3, which is much slower than natural flagellates (O(102 - 103) body lengths per minute). To investigate this, we applied theoretical and experimental methods, including fabrication of a swimmer that converts muscle contractions into large angular tail displacements, reaching swimming speeds of 86.8 m/s (0.58 body lengths per minute), surpassing low-Re predictions. Swimming dynamics sharply transition from a low-Re ([~] 10-3) to an intermediate-Re ([~] 0.1) regime when the actuation angle exceeded 4{degrees}. We used the swimmer to study the ability of muscle to adapt to mechanical stiffness and the beneficial effects of neuromuscular coculture on muscle development. These insights into mechanical and chemical cues will help optimize future biobots. TeaserHow are biological flagellate swimmers like E. coli and sperm cells so fast? We have built a new biohybrid robot to explore the theory.

bioengineering↗

bioRxiv2023

Synapses without tension fail to fire in an in vitro network of hippocampal neurons.

Neurons in the brain communicate with each other at their synapses. It has long been understood that this communication occurs through biochemical processes. Here, we reveal a previously unrecognized paradigm wherein mechanical tension in neurons is essential for communication. Using in vitro rat hippocampal neurons, we find that (1) neurons become tout/tensed after forming synapses resulting in a contractile neural network, and (2) without this contractility, neurons fail to fire. To measure time evolution of network contractility in 3D (not 2D) extracellular matrix, we developed an ultra-sensitive force sensor with 1 nN resolution. We employed Multi-Electrode Array (MEA) and iGluSnFR, a glutamate sensor, to quantify neuronal firing at the network and at the single synapse scale, respectively. When neuron contractility is relaxed, both techniques show significantly reduced firing. Firing resumes when contractility is restored. Neural contractility may play a crucial role in memory, learning, cognition, and various neuropathologies.

neuroscience↗