Abstract:
:The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Dasgupta S,Auth T,Gov NS,Satchwell TJ,Hanssen E,Zuccala ES,Riglar DT,Toye AM,Betz T,Baum J,Gompper Gdoi
10.1016/j.bpj.2014.05.024subject
Has Abstractpub_date
2014-07-01 00:00:00pages
43-54issue
1eissn
0006-3495issn
1542-0086pii
S0006-3495(14)00558-Xjournal_volume
107pub_type
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