Analysis of molecular movement reveals latticelike obstructions to diffusion in heart muscle cells
Ardo Illaste, Martin Laasmaa, Pearu Peterson, Marko Vendelin
Biophys J, 2012 Feb 22; 102(4): 739-48.
- PMID: 22385844
- DOI: 10.1016/j.bpj.2012.01.012
Significance
Molecules must move through heart cells to supply energy and coordinate responses to stress, yet their movement is slower than in a simple solution. This study combined fluorescence correlation spectroscopy measurements with a mathematical model to suggest why: cardiomyocytes may contain regularly spaced, low-permeability internal barriers about one micrometer apart. Such structures could restrict the diffusion of molecules involved in energy metabolism, reactive oxygen signaling, and cell death pathways. The findings identify cell architecture as a possible explanation for restricted molecular movement and help explain how structural changes in disease could alter cell function.
Abstract
Intracellular diffusion in muscle cells is known to be restricted. Although characteristics and localization of these restrictions is yet to be elucidated, it has been established that ischemia-reperfusion injury reduces the overall diffusion restriction. Here we apply an extended version of raster image correlation spectroscopy to determine directional anisotropy and coefficients of diffusion in rat cardiomyocytes. Our experimental results indicate that diffusion of a smaller molecule (1127 MW fluorescently labeled ATTO633-ATP) is restricted more than that of a larger one (10,000 MW Alexa647-dextran), when comparing diffusion in cardiomyocytes to that in solution. We attempt to provide a resolution to this counterintuitive result by applying a quantitative stochastic model of diffusion. Modeling results suggest the presence of periodic intracellular barriers situated ∼1 μm apart having very low permeabilities and a small effect of molecular crowding in volumes between the barriers. Such intracellular structuring could restrict diffusion of molecules of energy metabolism, reactive oxygen species, and apoptotic signals, enacting a significant role in normally functioning cardiomyocytes as well as in pathological conditions of the heart.