title: Stiffening of Red Blood Cells Induced by Cytoskeleton Disorders: A Joint Theory-Experiment Study.
abstract: The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bilayer. Among various cell types, the red blood cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two-dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria-infected RBCs (iRBCs) show that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the wormlike chain model for single spectrins and the effective medium theory for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with increasing end-to-end distances of spectrins, but has a nonmonotonic dependence on the variance of the end-to-end distance distributions. These predictions are verified quantitatively by our atomic force microscopy and micropipette aspiration measurements of iRBCs. The model may, from a molecular level, provide guidelines for future identification of new treatment methods for RBC-related diseases, such as malaria infection.
authors.affiliation: Singapore-Massachusetts Institute of Technology Alliance for Research and Technology Centre, Singapore; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Lai
authors.affiliation: Singapore-Massachusetts Institute of Technology Alliance for Research and Technology Centre, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Singapore-Massachusetts Institute of Technology Alliance for Research and Technology Centre, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore; Nano Biomechanics Laboratory, Department of Biomedical Engineering and Department of Mechanical Engineering, National University of Singapore, Singapore; Mechanobiology Institute, National University of Singapore, Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: Singapore-Massachusetts Institute of Technology Alliance for Research and Technology Centre, Singapore; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address: jianshu@mit.edu.
authors.forename: Jianshu
authors.initials: J
authors.lastname: Cao
mesh_terms: D001696:Biomechanical Phenomena; D003599:Cytoskeleton / Q000378:metabolism*; D004548:Elasticity; D004912:Erythrocytes / Q000166:cytology* / Q000473:pathology; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000166:cytology