An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite
An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite
The invasion of a merozoite into an erythrocyte by membrane wrapping is a hallmark of malaria pathogenesis. The invasion involves biomechanical interactions whereby the merozoite exerts actomyosin-based forces to push itself into and through the erythrocyte membrane while concurrently inducing biochemical damage to the erythrocyte membrane. Whereas the biochemical damage process has been investigated, the detailed mechanistic understanding of the invasion mechanics remains limited. Thus, the current study aimed to develop a mathematical model describing the mechanical factors involved in the merozoite invasion into an erythrocyte and explore the invasion mechanics.
A shell theory model was developed comprising constitutive, equilibrium and governing equations of the deformable erythrocyte membrane to predict membrane mechanics during the wrapping of an entire non-deformable ellipsoidal merozoite. Predicted parameters include principal erythrocyte membrane deformations and stresses, wrapping and indentation forces, and indentation work. The numerical investigations considered two limits for the erythrocyte membrane deformation during wrapping (4% and 51% areal strain) and erythrocyte membrane phosphorylation (decrease of membrane elastic modulus from 1 to 0.5 kPa).
For an intact erythrocyte, the maximum indentation force was 1 and 8.5 pN, and the indentation work was 1.92 × 10−18 and 1.40 × 10−17 J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 × 10−18 and 0.70 × 10−17 J for 4% and 51% areal strain.
The current study demonstrated the developed model's feasibility to provide new knowledge on the physical mechanisms of the merozoite invasion process that contribute to the invasion efficiency towards the discovery of new invasion-blocking anti-malaria drugs.
Malaria, Mathematical model, Phosphorylation, Red blood cell, Spectrin network
Msosa, Chimwemwe
1d20ea32-0103-4a15-a639-cd225f82539f
Abdalrahman, Tamer
65d60fa0-5278-4158-9e58-a75854a2c4c1
Franz, Thomas
31f508f4-6851-4274-b256-cc01ab321d50
April 2023
Msosa, Chimwemwe
1d20ea32-0103-4a15-a639-cd225f82539f
Abdalrahman, Tamer
65d60fa0-5278-4158-9e58-a75854a2c4c1
Franz, Thomas
31f508f4-6851-4274-b256-cc01ab321d50
Msosa, Chimwemwe, Abdalrahman, Tamer and Franz, Thomas
(2023)
An analytical model describing the mechanics of erythrocyte membrane wrapping during active invasion of a plasmodium falciparum merozoite.
Journal of the Mechanical Behavior of Biomedical Materials, 140, [105685].
(doi:10.1016/j.jmbbm.2023.105685).
Abstract
The invasion of a merozoite into an erythrocyte by membrane wrapping is a hallmark of malaria pathogenesis. The invasion involves biomechanical interactions whereby the merozoite exerts actomyosin-based forces to push itself into and through the erythrocyte membrane while concurrently inducing biochemical damage to the erythrocyte membrane. Whereas the biochemical damage process has been investigated, the detailed mechanistic understanding of the invasion mechanics remains limited. Thus, the current study aimed to develop a mathematical model describing the mechanical factors involved in the merozoite invasion into an erythrocyte and explore the invasion mechanics.
A shell theory model was developed comprising constitutive, equilibrium and governing equations of the deformable erythrocyte membrane to predict membrane mechanics during the wrapping of an entire non-deformable ellipsoidal merozoite. Predicted parameters include principal erythrocyte membrane deformations and stresses, wrapping and indentation forces, and indentation work. The numerical investigations considered two limits for the erythrocyte membrane deformation during wrapping (4% and 51% areal strain) and erythrocyte membrane phosphorylation (decrease of membrane elastic modulus from 1 to 0.5 kPa).
For an intact erythrocyte, the maximum indentation force was 1 and 8.5 pN, and the indentation work was 1.92 × 10−18 and 1.40 × 10−17 J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 × 10−18 and 0.70 × 10−17 J for 4% and 51% areal strain.
The current study demonstrated the developed model's feasibility to provide new knowledge on the physical mechanisms of the merozoite invasion process that contribute to the invasion efficiency towards the discovery of new invasion-blocking anti-malaria drugs.
Text
P073 manuscript Chim rev09 - UoS
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Restricted to Repository staff only until 4 February 2025.
More information
Accepted/In Press date: 23 January 2023
e-pub ahead of print date: 26 January 2023
Published date: April 2023
Additional Information:
Funding Information:
This research was supported financially by the National Research Foundation of South Africa (grants CPRR14071676206 and IFR14011761118 to TF ) and the South African Medical Research Council (grant SIR328148 to TF), and grants from the World Bank to the University of Malawi . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Any opinion, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily represent the official views of the funding agencies.
Publisher Copyright:
© 2023 Elsevier Ltd
Keywords:
Malaria, Mathematical model, Phosphorylation, Red blood cell, Spectrin network
Identifiers
Local EPrints ID: 484629
URI: http://eprints.soton.ac.uk/id/eprint/484629
ISSN: 1751-6161
PURE UUID: 39868861-ebdf-452f-8cf0-763907c1ecbb
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Date deposited: 17 Nov 2023 18:10
Last modified: 17 Mar 2024 01:39
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Contributors
Author:
Chimwemwe Msosa
Author:
Tamer Abdalrahman
Author:
Thomas Franz
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