Associate Professor National University of Singapore, United States
Introduction: Blood plasma has putatively been regarded as a Newtonian fluid comprising dilute concentrations (~10%) of proteins, electrolytes and immunoglobulins suspended in water. However, over the last decade, a handful of studies accessed the diminutive elastic properties of plasma with high sensitivity rheological measurement devices. However, there has been no comprehensive study investigating the source of this viscoelasticity, such as the effect of protein concentrations. This oft-neglected elastic rheological property may have potential bearing on cellular dynamics and distributions of red blood cells (RBCs) in the cardiovascular system, in turn influencing oxygen delivery by RBCs. This may be exacerbated in pathological conditions such as cardiovascular diseases and diabetes which are often accompanied by changes in plasma protein composition. In this study, we mechanistically investigated the relative contribution of several abundant plasma constituent proteins (albumin, fibrinogen and hemoglobin) to the bulk elastic properties of the solution. Engineered solutions containing physiological concentrations of the abovementioned proteins were characterized using a custom-built capillary breakup extensional rheometer.
Materials and
Methods: Protein solutions of varying concentrations were prepared by dissolving the proteins (albumin, fibrinogen and hemoglobin) in distilled water. The viscosities of the fluid samples were measured with a commercial rotational viscometer (DV2T, Brookfield Ametek, USA) at 25°C across three decades of shear rates within physiological ranges (10 to 1000 s-1). Relaxation times (indicating solution elasticity) were measured by a custom-built capillary breakup extensional rheometer at 25°C using a slow retraction method.
Results, Conclusions, and Discussions: Engineered solutions containing physiological concentrations of the abovementioned proteins were characterized to parametrically control the solution composition, and their viscoelastic properties were measured using the custom-built capillary breakup extensional rheometer. Three proteins were investigated based on their abundance in blood plasma and their high correlation to plasma relaxation time measured from mass spectrometry – albumin, fibrinogen and hemoglobin. Albumin and hemoglobin solutions were found to be purely viscous with no stable capillary filaments formed during the extension process. On the other hand, the fibrinogen solutions displayed not only a relaxation time similar to that measured with blood plasma, but also an apparent dose-dependent response. This is attributed to the long, branched structure of fibrinogen, which is capable of uncoiling in shear flow and storing elastic energy. Moving forward, we will be measuring mixtures of proteins to more closely mimic the complex protein composition of blood plasma. We will also be varying the base solvent in order to investigate the effect of electrostatic shielding.
