Spatial and Temporal Dynamics and Mechanical Properties of Human Erythrocytes: Impact on Microcirculation

Prof. Rafi Korenstein
Dept. of Physiology and Pharmacology, Sackler Faculty of Medicine,
Tel Aviv University

Blood microcirculation is determined to a large extent by red blood cell (RBC) deformability, plasma viscosity, and blood hematocrit. In microcirculation, the RBC bends and deforms upon entrance into a blood vessel capillary of a cross-section smaller than the largest diameter of the RBC (~8µ m). The current consensus is that cellular deformability of the RBC is determined only by its passive mechanical properties. According to this view, RBC fluctuations are caused solely by thermal energy. Our working hypothesis is that the dynamic mechanical properties of the red blood cell are determined to a large extent by a metabolically driven mechanical fluctuations of the membrane skeleton network. The existence of metabolic reactions can serve as an additional energy source for cellular deformation, acting to increase the ability of the cell to deform, enabling it to pass more efficiently through blood microcapillaries.

The long-term objective of our research is to elucidate the mechanisms underlying the active and passive mechanical properties of the RBC in order to understand the cellular parameters that determine RBC microcirculation and develop new ways to improve. The specific goals of our current research are:

  1. To determine the role of active (metabolically driven) and passive (thermally driven) driving forces in RBC deformability.
  2. To determine the modulation of the active (metabolically driven) components of cell deformability by plasma viscosity.
  3. To explore the molecular components involved in RBC surface fluctuations.
  4. To establish the relationship between the active and passive components which drive RBC deformability and filterability through narrow pores.

These studies are expected to pave new ways for improving blood flow under different physiological and pathological situations of impaired microcirculation.

An important aspect of our research is the further development of novel microscopic methodologies, such as Atomic Force Microscopy (AFM) and Point Dark Field Microscopy. This latter technique is a unique and new type of microscopy developed by our group. Its further development will enable its use in visualizing unstained subcellular membrane structures in the cytosol of living cells. This will undoubtedly shed considerable light on central problems in cell biology. The development of AFM methodology for studying micromechanical properties of cells and subcellular structures is a challenge at the cutting edge of science.