Cell-size heterogeneity acts as a regime-dependent mechanical switch for collective migration

Cell-size heterogeneity is ubiquitous in epithelial tissues, yet the fundamental physical principles governing its impact on collective migration remain elusive. Here, we show that size heterogeneity acts as a regime-dependent mechanical switch: it enhances collective motility in solid-like tissues while strongly suppressing migration in fluidized ones. This reversal arises from a previously unrecognized energetic hierarchy that governs microscopic topological remodeling. By systematically quantifying the work required for cellular neighbor exchanges, we demonstrate that size diversity reshapes the tissue energy landscape. In heterogeneous tissues, larger cells function as mechanically constrained anchors that elevate local rearrangement barriers, stabilizing the tissue against topological fluctuations. Crucially, these emergent energetic constraints either compete with or reinforce shape-based structural changes depending on the mechanical state, dictating the overall rate of tissue remodeling. Together, our results establish a unified physical framework linking microscale size heterogeneity to the fundamental energetic cost of cell rearrangements and suggest that cell-size distribution serves as an intrinsic tunable parameter that dictates the epithelial mechanical property and migratory potential across diverse physiological contexts.