Continuous force-displacement relationships for the human red blood cell at different erythrocytic developmental stages
- PDF / 151,197 Bytes
- 6 Pages / 612 x 792 pts (letter) Page_size
- 97 Downloads / 215 Views
Y7.8.1
Continuous force-displacement relationships for the human red blood cell at different erythrocytic developmental stages of Plasmodium falciparum malaria parasite John P. Mills1, Lan Qie3, Ming Dao1, Kevin S. W. Tan4, Chwee Teck Lim3 and Subra Suresh1,2 1 Department of Materials Science and Engineering, 2Division of Biological Engineering and Affiliated Faculty of the Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. 3 Division of Bioengineering, 4Department of Microbiology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 117576. Republic of Singapore. ABSTRACT Prior work involving either aspiration of infected cells into micropipette under suction pressure or deformation in laminar shear flow revealed that the malaria parasite Plasmodium (P.) falciparum could result in significant stiffening of infected human red blood cells (RBCs). In this paper, we present optical tweezers studies of progressive changes to nonlinear mechanical response of infected RBCs at different developmental stages of P. falciparum. From early ring stage to late trophozoite and schizont stages, up to an order of magnitude increase in shear modulus was found under controlled mechanical loading by combining experiments with threedimensional computational simulations. These results provide novel approaches to study changes in mechanical deformability in the advanced stages of parasite development in the erythrocyte, and suggest a significantly greater stiffening of the red blood cell due to P. falciparum invasion than that considered from previous studies. INTRODUCTION The architecture of the human RBC (erythrocyte), without a nucleus or internal organelles and with a well-defined biconcave shape, presents a relatively simple model system, compared to other biological cells, for the study of single-cell mechanics. The RBC membrane enclosing the cytosol consists of a phospholipid bilayer supported by a complex cytoskeletal network which comprises spectrin molecules anchored at actin nodes, and proteins 4.1, 4.2, ankyrin and adducin [1, 2]. Interactions involving ankyrin, the RBC anion transporter band 3, protein 4.1 and sialoglycoproteins such as glycoprotein A facilitate connections between phospholipid membrane and cytoskeleton. The cytoskeletal network facilitates deformability of the RBC that permits its biological function of transporting oxygen and carbon dioxide. With a biconcave or discocyte shape and a diameter of about 8 µm, the RBC passes through narrow capillaries with inner diameters as small as 3 µm. There it undergoes large, reversible, nonlinear elastic deformation with strains in excess of 100%. The RBC also severely deforms through intercellular gaps of sinusoids in the spleen where stiffened and aged RBCs are removed. This deformability is severely hampered by the P. falciparum parasite, the deadliest of the four species of malaria, which results in two to three million deaths annually [1]. When an RBC is i
Data Loading...
