title: Anomalous diffusion induced by cristae geometry in the inner mitochondrial membrane.
abstract: Diffusion of inner membrane proteins is a prerequisite for correct functionality of mitochondria. The complicated structure of tubular, vesicular or flat cristae and their small connections to the inner boundary membrane impose constraints on the mobility of proteins making their diffusion a very complicated process. Therefore we investigate the molecular transport along the main mitochondrial axis using highly accurate computational methods. Diffusion is modeled on a curvilinear surface reproducing the shape of mitochondrial inner membrane (IM). Monte Carlo simulations are carried out for topologies resembling both tubular and lamellar cristae, for a range of physiologically viable crista sizes and densities. Geometrical confinement induces up to several-fold reduction in apparent mobility. IM surface curvature per se generates transient anomalous diffusion (TAD), while finite and stable values of projected diffusion coefficients are recovered in a quasi-normal regime for short- and long-time limits. In both these cases, a simple area-scaling law is found sufficient to explain limiting diffusion coefficients for permeable cristae junctions, while asymmetric reduction of the junction permeability leads to strong but predictable variations in molecular motion rate. A geometry-based model is given as an illustration for the time-dependence of diffusivity when IM has tubular topology. Implications for experimental observations of diffusion along mitochondria using methods of optical microscopy are drawn out: a non-homogenous power law is proposed as a suitable approach to TAD. The data demonstrate that if not taken into account appropriately, geometrical effects lead to significant misinterpretation of molecular mobility measurements in cellular curvilinear membranes.
authors.affiliation: Kinematic Cell Research, Institute for Cell Biology and Neurosciences, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. sukhorukov@kizefo.de
authors.forename: Valerii M
authors.initials: VM
authors.lastname: Sukhorukov
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bereiter-Hahn
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D006801:Humans; D051336:Mitochondrial Membranes / Q000648:ultrastructure*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D021381:Protein Transport
chemical_list: D024101:Mitochondrial Proteins