Cytoplasmic fluidity couples nutrient availability and enterocyte fate in vivo

Cells must continuously adapt their internal state to fluctuating nutritional environments. For the adaptation, cells sense distinct nutrients through specific molecular signals, such as the insulin and mTOR pathways. Here, in addition to the conventional nutrient-sensing mechanisms, we reveal a mechanistic layer by which gut enterocytes respond to dietary contents, demonstrating that nutritional components in food regulate cytoplasmic fluidity, a fundamental biophysical property and determine cellular status. We found that the quantity, rather than the quality, of amino acids alters the nanoscale cytoplasmic fluidity in Drosophila enterocytes and the frequency of erebosis, a nonapoptotic cell death mediating intestinal cell turnover. Manipulating cytoplasmic fluidity through several independent inert small viscogen molecules affects erebosis, indicating that intracellular fluidity can directly control cell fate decisions. We propose that intracellular nanoscale fluidity represents a fundamental principle for enterocytes to detect and adapt to dietary components, providing a biophysical basis for cellular homeostasis in vivo.