Tensile forces and shape entropy explain observed crista structure in mitochondria

We present a model from which the observed morphology of the inner mitochondrial membrane can be inferred as minimizing the system's free energy. In addition to the usual energetic terms for bending, surface area, and pressure difference, our free energy includes terms for tension that we hypothesize to be exerted by proteins and for an entropic contribution due to many dimensions worth of shapes available at a given energy. We also present measurements of the structural features of mitochondria in HeLa cells and mouse embryonic fibroblasts using three-dimensional electron tomography. Such tomograms reveal that the inner membrane self-assembles into a complex structure that contains both tubular and flat lamellar crista components. This structure, which contains one matrix compartment, is believed to be essential to the proper functioning of mitochondria as the powerhouse of the cell. Interpreting the measurements in terms of the model, we find that tensile forces of ∼20 pN would stabilize a stress-induced coexistence of tubular and flat lamellar cristae phases. The model also predicts a pressure difference of -0.036 ± 0.004 atm (pressure higher in the matrix) and a surface tension equal to 0.09 ± 0.04 pN/nm.