biophysics of malarial parasite exit from infected erythrocytes生物物理学的疟原虫退出感染的红细胞.pdfVIP

Biophysics of Malarial Parasite Exit from Infected Erythrocytes 1 2¤ 1 1 3 1 Rajesh Chandramohanadas , YongKeun Park , Lena Lui , Ang Li , David Quinn , Kingsley Liew , 3 2 3 4 5 Monica Diez-Silva , Yongjin Sung , Ming Dao *, Chwee Teck Lim , Peter Rainer Preiser *, Subra Suresh1,3 1 Singapore-MIT Alliance for Research and Technology Centre, Singapore, Singapore, 2 George R. Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 4 National University of Singapore, Singapore, Singapore, 5 Nanyang Technological University, Singapore, Singapore Abstract Upon infection and development within human erythrocytes, P. falciparum induces alterations to the infected RBC morphology and bio-mechanical properties to eventually rupture the host cells through parasitic and host derived proteases of cysteine and serine families. We used previously reported broad-spectrum inhibitors (E64d, EGTA-AM and chymostatin) to inhibit these proteases and impede rupture to analyze mechanical signatures associated with parasite escape. Treatment of late-stage iRBCs with E64d and EGTA-AM prevented rupture, resulted in no major RBC cytoskeletal reconfiguration but altered schizont morphology followed by dramatic re-distribution of three-dimensional refractive index (3D-RI) within the iRBC. The