Red blood cell thickness is evolutionarily constrained by slow, hemoglobin-restricted diffusion in cytoplasm

Area of Science:

• Physiology
• Biophysics
• Cell Biology

Background:

• Red blood cells (RBCs) rapidly exchange gases during capillary transit.
• Intracellular diffusion limitations within RBCs are not well understood.
• RBC shape and intracellular properties may influence gas exchange efficiency.

Purpose of the Study:

• To quantify carbon dioxide (CO2) diffusivity within human RBCs.
• To investigate the relationship between CO2 diffusivity and RBC intracellular properties, specifically mean corpuscular hemoglobin concentration (MCHC).
• To correlate RBC cytoplasmic diffusion rates with RBC shape and thickness across species.

Main Methods:

• CO2 diffusivity (DCO2) was measured in RBCs using fluorescence imaging of intracellular [H+] dynamics.
• The method relies on H+ diffusion being facilitated by the CO2/HCO3- buffer system.
• DCO2 was assessed in relation to varying hemoglobin concentrations and cell thickness.

Main Results:

• CO2 diffusivity within human RBCs was found to be significantly restricted, only 5% of the rate in water.
• DCO2 decreased by half for every 75 g/L increase in MCHC.
• An inverse relationship exists between MCHC and RBC thickness across >250 animal species.

Conclusions:

• Cytoplasmic diffusion of CO2 in RBCs is a significant physiological limitation.
• RBC thickness is inversely proportional to MCHC, likely as an adaptation to restricted CO2 diffusion.
• Cellular morphology is crucial for maintaining efficient gas exchange given intracellular diffusion constraints.