Universal physical responses to stretch in the living cell

Abstract

How do cells in our body go about their routine mechanical business of stretching, contracting and remodelling? This question has far-reaching implications for understanding airway narrowing in asthma, cell invasion in cancer and vessel constriction in cardiovascular disease. The answer, arrived at in a novel experimental system measuring the 'stretch' of human airway smooth muscle cells, is that the cell has much in common with familiar materials including tomato ketchup, shaving foam and toothpaste. These materials fluidize when deformed, as do granular materials including sugar in a bowl or coffee beans. Such materials act as a glass-like intermediate form of matter, neither solid nor fluid but retaining features of both. How the cell goes about its routine mechanical business of stretching, contracting, and remodelling has implications for understanding excessive airway narrowing in asthma, cell invasion in cancer and vessel constriction in vascular disease. Surprisingly, the cell is an intermediate form of matter, neither solid nor fluid but retaining features of both - that responds to stretch by fluidizing, much as do common pastes, foams, clays, and colloids. With every beat of the heart, inflation of the lung or peristalsis of the gut, cell types of diverse function are subjected to substantial stretch. Stretch is a potent stimulus for growth, differentiation, migration, remodelling and gene expression1,2. Here, we report that in response to transient stretch the cytoskeleton fluidizes in such a way as to define a universal response class. This finding implicates mechanisms mediated not only by specific signalling intermediates, as is usually assumed, but also by non-specific actions of a slowly evolving network of physical forces. These results support the idea that the cell interior is at once a crowded chemical space3 and a fragile soft material in which the effects of biochemistry, molecular crowding and physical forces are complex and inseparable, yet conspire nonetheless to yield remarkably simple phenomenological laws. These laws seem to be both universal and primitive, and thus comprise a striking intersection between the worlds of cell biology and soft matter physics.