title: In vivo volume and hemoglobin dynamics of human red blood cells.
abstract: Human red blood cells (RBCs) lose ∼30% of their volume and ∼20% of their hemoglobin (Hb) content during their ∼100-day lifespan in the bloodstream. These observations are well-documented, but the mechanisms for these volume and hemoglobin loss events are not clear. RBCs shed hemoglobin-containing vesicles during their life in the circulation, and this process is thought to dominate the changes in the RBC physical characteristics occurring during maturation. We combine theory with single-cell measurements to investigate the impact of vesiculation on the reduction in volume, Hb mass, and membrane. We show that vesicle shedding alone is sufficient to explain membrane losses but not volume or Hb losses. We use dry mass measurements of human RBCs to validate the models and to propose that additional unknown mechanisms control volume and Hb reduction and are responsible for ∼90% of the observed reduction. RBC population characteristics are used in the clinic to monitor and diagnose a wide range of conditions including malnutrition, inflammation, and cancer. Quantitative characterization of cellular maturation processes may help in the early detection of clinical conditions where maturation patterns are altered.
authors.affiliation: Center for Systems Biology and Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Roy
authors.initials: R
authors.lastname: Malka
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Francisco Feijó
authors.initials: FF
authors.lastname: Delgado
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Manalis
authors.affiliation: Center for Systems Biology and Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Higgins
mesh_terms: D019295:Computational Biology; D022162:Cytoplasmic Vesicles; D004911:Erythrocyte Volume / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology* / Q000502:physiology*; D006454:Hemoglobins / Q000502:physiology*; D006801:Humans
chemical_list: D006454:Hemoglobins