Pairing computational and scaled physical models to determine permeability as a measure of cellular communication in micro- and nano-scale pericellular spaces

Cells, the living components of tissues, bathe in fluid. The pericellular fluid environment is a challenge to study due to the remoteness and complexity of its nanoscale fluid pathways. The degree to which the pericellular fluid environment modulates the transport of mechanical and molecular signals between cells and across tissues is unknown. As a consequence, experimental and computational studies have been limited and/or highly idealized. In this study we apply a fundamental fluid dynamics technique to measure pericellular permeability through scaled-up physical models obtained from high resolution microscopy. We assess permeability of physiologic tissue by tying together data from parallel experimental and computational models that account for specific structures of the flow cavities and cellular structures therein (cell body, cell process, pericellular matrix). A healthy cellular network devoid of cellular structure is shown to exhibit permeability on the order of 2.8 x 10(-16) m(2) inclusion of cellular structures reduces permeability to the order of 10(-17) to 10(-18) m(2). These permeability studies provide not only unprecedented quantitative experimental measures of the pericellular fluid environment but also provide a novel measure of "infrastructural integrity" that likely influences the efficiency of the cellular communication network across the tissue.