Interfacial Energy Balance Governs Initial Cell Spreading Dynamics

Cell spreading is a fundamental process in physiological and pathological contexts, including tissue formation, wound healing, and cancer cell extravasation. Previous studies have examined biophysical mechanisms governing early spreading (around 1-10 min) while biomolecular processes also begin to emerge, yet initial spreading in an even earlier stage (<1 min) remains largely unexplored. Here, we present a deterministic model based on interfacial energy balance─integrating strain energy, surface adhesion energy, and viscous dissipation─to quantitatively describe initial spreading dynamics. Using interference reflection microscopy (IRM), we characterize spreading behaviors of three breast cell lines (MCF-10A, MCF-7, and MDA-MB-231) on extracellular matrix-coated substrates. Model predictions, incorporating biomechanical and biochemical parameters measured through IRM and atomic force microscopy (AFM), show strong agreements with experimental observations. This work provides a universal framework for understanding initial spreading and offers insights into strategies to regulate initial cell spreading, with potential applications in cancer treatment and tissue engineering.