Network thermodynamic model of coupled transport in a multicellular tissue--the islet of Langerhans.

Network thermodynamic modeling via bond graphs was used to describe the water and cryoprotectant additive (CPA) transport in a multicellular tissue. The model is presented as a tool to understand the osmotic behavior of the islets of Langerhans when exposed to ternary aqueous solutions containing an electrolyte and a CPA. It accounts for the effects of the location of cells within the tissue and an interstitial matrix, plus differential permeabilities to water and CPA. The interstitial matrix was assumed to be a porous medium able to store the chemical species being transported. Controlled osmotic stress experiments were conducted on isolated rat pancreas islets to measure the transient volumetric response to step-wise changes in dimethyl sulfoxide, Me2SO, concentration. The model provides a tool for predicting the transient volumetric response of peripheral and interior cells and of interstitial tissue, as well as the build up of solute concentration, during addition and removal of CPAs and freezing and thawing protocols. Inverse solution methods were applied to determine values for standard cell membrane permeability parameters Lp, omega and sigma as well as for the interstitial flow conductivities Kw and Kp'.

Osmotic behavior and transport properties of human islets in a dimethyl sulfoxide solution.

The osmotic responses of isolated human islets were evaluated using a perfusion cryomicroscope device. Individual islet volumes were measured following equilibration with a series of solutions of graded solute concentration. The osmotically inactive volume for human islets was determined to be 25% from a Boyle-van't Hoff plot of these data. A network thermodynamic model was developed via the bond graph method to describe the transport of water and cryoprotective agent in pancreatic islets. The model was curve fit to transient volumetric data for the response of islets to a stepwise exposure to 1 Me2SO at temperatures of 24.0, 3.0, or -3.5 degrees C. Standard membrane transport parameters (Lp, omega, sigma) and interstitial diffusion transport properties (kappa w, kappa p) were calculated from the fitting procedure. The temperature coefficients for membrane transport properties were expressed in terms of activation energies for water (ELp) and Me2SO (E omega). Osmotic challenge experiments conducted with fresh and cryopreserved human islets indicate that frozen/thawed islets exhibit a a slight increase in transport properties.