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Biophysical Tools and Concepts Enable Understanding of Asexual Blood Stage Malaria.

Published version
Peer-reviewed

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Authors

Introini, Viola 
Govendir, Matt A 
Rayner, Julian C 
Cicuta, Pietro 
Bernabeu, Maria 

Abstract

Forces and mechanical properties of cells and tissues set constraints on biological functions, and are key determinants of human physiology. Changes in cell mechanics may arise from disease, or directly contribute to pathogenesis. Malaria gives many striking examples. Plasmodium parasites, the causative agents of malaria, are single-celled organisms that cannot survive outside their hosts; thus, thost-pathogen interactions are fundamental for parasite's biological success and to the host response to infection. These interactions are often combinations of biochemical and mechanical factors, but most research focuses on the molecular side. However, Plasmodium infection of human red blood cells leads to changes in their mechanical properties, which has a crucial impact on disease pathogenesis because of the interaction of infected red blood cells with other human tissues through various adhesion mechanisms, which can be probed and modelled with biophysical techniques. Recently, natural polymorphisms affecting red blood cell biomechanics have also been shown to protect human populations, highlighting the potential of understanding biomechanical factors to inform future vaccines and drug development. Here we review biophysical techniques that have revealed new aspects of Plasmodium falciparum invasion of red blood cells and cytoadhesion of infected cells to the host vasculature. These mechanisms occur differently across Plasmodium species and are linked to malaria pathogenesis. We highlight promising techniques from the fields of bioengineering, immunomechanics, and soft matter physics that could be beneficial for studying malaria. Some approaches might also be applied to other phases of the malaria lifecycle and to apicomplexan infections with complex host-pathogen interactions.

Description

Keywords

Plasmodium, biophysics, cytoadhesion, imaging, malaria, mechanobiology, microfluidics, Erythrocytes, Humans, Life Cycle Stages, Malaria, Plasmodium falciparum, Protozoan Proteins

Journal Title

Front Cell Infect Microbiol

Conference Name

Journal ISSN

2235-2988
2235-2988

Volume Title

12

Publisher

Frontiers Media SA
Sponsorship
Engineering and Physical Sciences Research Council (EP/R011443/1)
Wellcome Trust (220266/Z/20/Z)