Single-cell O 2 exchange imaging shows that cytoplasmic diffusion is a dominant barrier to efficient gas transport in red blood cells

• DOI: 10.1073/pnas.1916641117
• Publication Date: 2020-04-23T00:10:50Z
• Authors: Sarah L. Richardson; Alzbeta Hulikova; Melanie Proven; Ria Hipkiss; Magbor Akanni; Noémi B. A. Roy; Pawel Swietach
• Keywords: Adult; Male; Cytoplasm; 0303 health sciences; Erythrocytes; Biological Transport; Biological Sciences; Carbon Dioxide; Middle Aged; Healthy Volunteers; 3. Good health; Oxygen; Hemoglobins; 03 medical and health sciences; Humans; Female; Gases; Single-Cell Analysis; Aged

Significance Blood is routinely tested for gas-carrying capacity (total hemoglobin), but this cannot determine the speed at which red blood cells (RBCs) exchange gases. Such information is critical for evaluating the physiological fitness of RBCs, which have very limited capillary transit times (<1 s) for turning over substantial volumes of gas. We developed a method to quantify gas exchange in individual RBCs and used it to show that restricted diffusion, imposed by hemoglobin crowding, is a major barrier to gas flows. Consequently, hematological disorders manifesting a change in cell shape or hemoglobin concentration have uncharted implications on gas exchange, which we illustrate using inherited anemias. With its single-cell resolution, the method can identify physiologically inferior subpopulations, providing a clinically useful appraisal of blood quality.