Biology subjects

Abdalrahman, T.

Publications and source records attributed to Abdalrahman, T..

13 recordsLinked to original sources

bioRxiv2025

Impact of modification of envelope proteins on the mechanical properties of HIV virus-like particles

The mechanical interactions between virus-like particles and host cells may offer targets for new viral treatments and vaccines with modes of action that are independent of the immune system. The physical properties of structures involved govern the particle-cell interactions. While the mechanical properties of virions and mammalian cells have been widely studied, data on virus-like particles are limited. This study aimed to determine the mechanical and morphological properties of HIV-1 virus-like particles with different envelopes. Three HIV-like particles, i.e. GagM + gp150, GagM + gp140HA2tr, and GagM + gp120HA2, were produced by combining the same Gag protein shell with different trimeric glycoprotein envelopes. The particles spring constant, breaking force, and dimensions were determined using atomic force microscopy, and the elastic modulus was quantified using finite element analysis. Spring constant, elastic modulus, and breaking force were higher for GagM + gp140HA2tr and GagM + gp120HA2 than for GagM + gp150. The particle height was smaller for GagM + gp120HA2 than for GagM + gp150 and GagM + gp140HA2tr. Possible mechanisms underlying the increase of the particles stiffness and mechanical strength are the inclusion of the influenza virus HA transmembrane domain in the HIV Env protein, and the lower expression and packing density of Env in GagM + gp140HA2tr and GagM + gp120HA2 compared to GagM + gp150 found previously. Upon confirmation, the proposed mechanisms offer potential to tailor the mechanics of HIV virus-like particles and guide mechanical interactions between VLPs and host cells towards improving vaccines.

biophysics↗

bioRxiv2025

In silico analysis of the invasion mechanics and invasiveness of the plasmodium falciparum merozoite

Although there has been considerable progress in understanding the factors that determine the invasiveness of plasmodium falciparum merozoites, the collective role of the biophysical characteristics of erythrocyte deformability in the invasion process is poorly understood. Cell shape, cytoplasmic viscosity, and membrane stability are the main determinants of erythrocyte deformability, but it remains unknown how these properties affect the merozoite invasiveness. This study aimed to investigate computationally (i) the role of erythrocyte morphology and merozoite-induced erythrocyte membrane damage in merozoite invasion and (ii) the suitability of mechanical markers of merozoite-induced erythrocyte membrane damage for screening of invasion-blocking antimalarial drugs. Finite element models were developed to represent a human erythrocyte and a spherocyte, their invasion by a malaria merozoite, and erythrocyte compression and nanoindentation as mechanical assays for membrane damage. Smoothed particle hydrodynamics represented the erythrocyte cytoplasm, and merozoite-induced erythrocyte membrane damage was implemented with a constitutive model. The invasiveness of the merozoite decreases with increased erythrocyte sphericity associated with genetic disorders such as hereditary spherocytosis. The invasiveness is larger when membrane damage is induced in the erythrocyte at an early invasion stage than throughout the invasion process. The minimum force required for a malaria merozoite to invade a human erythrocyte was predicted to be 11 pN. The findings on the invasion mechanics can guide future studies into the invasiveness of the merozoite. The nanoindentation simulations point to the potential of nanoindentation to determine erythrocyte membrane damage for screening novel invasion-blocking anti-malaria drugs.

bioengineering↗

bioRxiv2025

A Mathematical Model for Chemo-mechanically Induced Collective Cell Motility on Planar Elastic Substrates

Cells interact with mechanical and chemical environmental cues, such as mechanical cues from other cells and chemical signals from growth factors. The current study aims to develop a mathematical model for combined chemically and mechanically induced collective cell motility on planar substrates. The mechanically induced cell motility is simulated using strain energy density gradients generated in an elastic substrate by cellular traction forces. For chemotaxis, Greens function and Duhamels principle are used to solve the diffusion equation that describes the distribution of a growth factor and to represent chemo-mechanically induced deterministic collective cell motility on planar elastic substrates. Chemically induced motility of cells towards a growth factor source is predicted for different growth factor production and diffusion rates. Chemo-mechanical cues with varying growth factor production and diffusion rates are explored for the motility of four cells and one motile cell in the presence of one stationary cell. The developed model describes the chemo-mechanically induced motility of individual cells on planar substrates. The model provides valuable information for in vivo or in vitro studies due to its suitability for extension to other chemical source shapes, mobilised sources, many sources, and soluble concentration gradients.

biophysics↗

bioRxiv2023

A constitutive model for the remodelling erythrocyte membrane skeleton during the active invasion by the malaria merozoite

Malaria merozoites phosphorylate erythrocyte membrane proteins to breach the membrane during invasion. This study aimed to develop a constitutive model for erythrocyte membrane phosphorylation that reduces the membranes elastic modulus and resistance to merozoite invasion. The hyperelastic Mooney Rivlin constitutive model was adapted by adding an exponential term to represent the mechanical effect of erythrocyte membrane phosphorylation. The modified algorithm was verified with the unmodified Mooney Rivlin model for the intact erythrocyte membrane and used to predict erythrocyte membrane stress for equi-biaxial membrane strain up to 1.1 for different severity of phosphorylation damage. The stability of the damage model was assessed using the Drucker criterion for equi-biaxial strain up to 2.0. Strain and stress predicted with the developed damage model and the Mooney Rivlin model agreed for the intact erythrocyte membrane. The membrane stress at a strain of 1.1 decreased by 42% for minor and 95% for severe erythrocyte membrane damage. The stability strain threshold of the damage model was 1.98 for minor and 1.19 for severe membrane damage. The developed model can represent different degrees of erythrocyte membrane damage through phosphorylation by a malaria merozoite. The model will enable in silico investigations of the invasiveness of malaria merozoites.

biophysics↗

bioRxiv2023

In silico mechanics and TGF-β expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction

PurposeBiomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation of stem cells injected with the biomaterial into the infarcted heart. MethodsA microstructural finite element model of a mid-wall infarcted myocardial region was developed from ex vivo microcomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa. ResultsThe transplanted cells deformation was largest for Einj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einj changes for softer (Einj [≤] 738 kPa) than stiffer biomaterials. ConclusionsCombining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The approach offers a broader scope for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

bioengineering↗

bioRxiv2022

Mathematical Model of Mechanosensing and Mechanically Induced Collective Motility of Cells on Planar Elastic Substrates

Cells mechanically interact with their environment to sense, for example, topography, elasticity and mechanical cues from other cells. Mechano-sensing has profound effects on cellular behaviour, including motility. The current study aims to develop a mathematical model of cellular mechano-sensing on planar elastic substrates and demonstrate the models predictive capabilities for the motility of individual cells in a colony. In the model, a cell is assumed to transmit an adhesion force, derived from a dynamic focal adhesion integrin density, that locally deforms a substrate, and to sense substrate deformation originating from neighbouring cells. The substrate deformation from multiple cells is expressed as total strain energy density with a spatially varying gradient. The magnitude and direction of the gradient at the cell location define the cell motion. Cell-substrate friction, partial motion randomness, and cell death and division are included. The substrate deformation by a single cell and the motility of two cells are presented for several substrate elasticities and thicknesses. The collective motility of 25 cells on a uniform substrate mimicking the closure of a circular wound of 200 m is predicted for deterministic and random motion. Cell motility on substrates with varying elasticity and thickness is explored for four cells and 15 cells, the latter again mimicking wound closure. Wound closure by 45 cells is used to demonstrate the simulation of cell death and division during migration. The mathematical model can adequately simulate the mechanically-induced collective cell motility on planar elastic substrates. The model is suitable for extension to other cell and substrates shapes and the inclusion of chemotactic cues, offering the potential to complement in vitro and in vivo studies.

biophysics↗

bioRxiv2022

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 x10-18 and 1.40 x10-17 J for 4% and 51% areal membrane strain. Phosphorylation damage in the erythrocyte membrane reduced the required indentation work by 50% to 0.97 x10-18 and 0.70 x10-17 J for 4% and 51% areal strain. The current study demonstrated the developed models 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.

biophysics↗

bioRxiv2022

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments

Cell stiffness and T-box transcription factor 3 (TBX3) expression have been identified as biomarkers of melanoma metastasis in 2D environments. This study aimed to determine how mechanical and biochemical properties of melanoma cells change during cluster formation in 3D environments. Vertical growth phase (VGP) and metastatic (MET) melanoma cells were embedded in 3D collagen matrices of 2 and 4 mg/ml collagen concentrations, representing low and high matrix stiffness. Mitochondrial fluctuation, intracellular stiffness, and TBX3 expression were quantified before and during cluster formation. In isolated cells, mitochondrial fluctuation decreased and intracellular stiffness increased with increase in disease stage from VGP to MET and increased matrix stiffness. TBX3 was highly expressed in soft matrices but diminished in stiff matrices for VGP and MET cells. Cluster formation of VGP cells was excessive in soft matrices but limited in stiff matrices, whereas for MET cells it was limited in soft and stiff matrices. In soft matrices, VGP cells did not change the intracellular properties, whereas MET cells exhibited increased mitochondrial fluctuation and decreased TBX3 expression. In stiff matrices, mitochondrial fluctuation and TBX3 expression increased in VGP and MET, and intracellular stiffness increased in VGP but decreased in MET cells. The findings suggest that soft extracellular environments are more favourable for tumour growth, and high TBX3 levels mediate collective cell migration and tumour growth in the earlier VGP disease stage but play a lesser role in the later metastatic stage of melanoma. Symbols O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/495509v4_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1444cf4org.highwire.dtl.DTLVardef@118427eorg.highwire.dtl.DTLVardef@1b56a0aorg.highwire.dtl.DTLVardef@144d41f_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

Decreased cell stiffness facilitates cell detachment and cell migration from breast cancer spheroids in 3D collagen matrices of different rigidity

BackgroundTumour-cell detachment is a critical early event in the metastatic cascade. However, the role of the cells mechanical properties in detachment and migration is not well understood. This exploratory study aimed to assess how intracellular stiffness changes these processes. MethodsMDA-MB-231 cells were embedded as 10,000-cell spheroids in 2 and 4 mg/ml collagen matrices. Intracellular stiffness was assessed with mitochondria tracking microrheology of cells that migrated distances equivalent to four and six times the cell diameter (dC) from the spheroid and compared to cells at the spheroid surface (0dC), representing medium, high and no migration, respectively. Results and discussionThe mitochondrial mean square displacement and intracellular stiffness decreased during detachment and migration for both collagen concentrations (i.e. rigidities). The mean square displacement of 4dC and 6dC cells was similar, whereas cell stiffness was lower for 4dC than for 6dC cells. With increasing matrix rigidity, the intracellular stiffness decreased for 0dC cells and did not change for 4dC and 6dC cells. It is proposed that decreased cell stiffness drives detachment and migration and increased matrix rigidity physically hinders migration, and cells need to become softer or remodel the environment to migrate. The independence of the stiffness of migrated cells from matrix rigidity suggests that cells remodel their environment through matrix proteins cleavage to migrate. ConclusionsThe study revealed the collective effects of enhanced migratory conditions and increased matrix rigidity on the mechanical properties of the cells. The expression of matrix metalloproteinases and transforming growth factor {beta} and the role of cell volume on detachment and migration in matrices with varying pore sizes are proposed targets for further studies on metastatic cancer cells.

cancer biology↗

bioRxiv2020

Micromechanical homogenisation of a hydrogel-filled electrospun scaffold for tissue-engineered epicardial patching of the infarcted heart

This study aimed at developing a formulation to link microscopic structure and macroscopic mechanics of a fibrous scaffold filled with a hydrogel for use as a tissue-engineered patch for local epicardial support of the infarcted heart. Mori-Tanaka mean field homogenisation, closed-cell foam mechanics and finite element (FE) methods were used to represent the macroscopic elastic modulus of the filled fibrous scaffold. The homogenised constitutive description of the scaffold was implemented for an epicardial patch in a FE model of a human cardiac left ventricle (LV) to assess effects of patching on myocardial mechanics and ventricular function in presences of an infarct. The macroscopic elastic modulus of the scaffold was predicted to be 0.287 MPa with the FE method and 0.290 MPa with the closed-cell model for the realistic fibre structure of the scaffold, and 0.108 and 0.540 MPa with mean field homogenization for randomly oriented and completely aligned fibres. Epicardial patching was predicted to reduce maximum myocardial stress in the infarcted LV from 19 kPa (no patch) to 9.5 kPa (patch), and to increase the ventricular ejection fraction from 40% (no patch) to 43% (patch). The predictions of the macroscopic elastic modulus of the realistic scaffold with the FE and the closed-cell model agreed well, and were bound by the mean field homogenisation prediction for random and fully aligned fibre orientation of the scaffold. This study demonstrates the feasibility of homogenization techniques to represent complex multiscale structural features in an simplified but meaningful manner.

bioengineering↗

bioRxiv2020

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

The formation of membrane protrusions during migration is reliant upon the cells cytoskeletal structure and stiffness. It has been reported that actin disruption blocks protrusions and decreases cell stiffness whereas microtubule disruption blocks protrusion but increases stiffness in several cell types. In melanoma, cell migration is of concern as this cancer spreads unusually rapidly during early tumour development. The aim of this study was to characterise motility, structural properties and stiffness of human melanoma cells at radial growth phase (RGP), vertical growth phase (VGP), and metastatic stage (MET) in two-dimensional in vitro environments. Wound assays, western blotting and mitochondrial particle tracking were used to assess cell migration, cytoskeletal content and intracellular fluidity. Our results indicate that cell motility increase with increasing disease stage. Despite their different motility, RGP and VGP cells exhibit similar fluidity, actin and tubulin levels. MET cells, however, display increased fluidity which was associated with increased actin and tubulin content. Our findings demonstrate an interplay between actin and microtubule activity and their role in increasing motility of cells while minimizing cell stiffness at advanced disease stage. In earlier disease stages, cell stiffness may however not serve as an indicator of migratory capabilities.

cancer biology↗

bioRxiv2019

Mathematical Model of Mechanical Virion-Cell Interaction During Early Engulfment in HIV

Viral endocytosis involves elastic cell deformation, driven by chemical adhesion energy, and depends on physical interactions between virion and cell membrane. These interactions are not easy to quantify experimentally. Hence, this study aimed to develop a mathematical model of the interactions of HIV particles with host cells and explore the effects of mechanical and morphological parameters during full virion engulfment. The invagination force and engulfment energy were described as viscoelastic and linear-elastic functions of radius and elastic modulus of virion and cell, ligand-receptor energy density and engulfment depth. The influence of changes in the virion-cell contact geometry representing different immune cells and ultrastructural membrane features and the decrease in virion radius and shedding of gp120 proteins during maturation on invagination force and engulfment energy was investigated. A low invagination force and high ligand-receptor energy are associated with high virion entry ability. The required invagination force was the same for immune cells of different sizes but lower for a local convex geometry of the cell membrane at the virion length scale. This suggests that localized membrane features of immune cells play a role in viral entry ability. The available engulfment energy decreased during virion maturation, indicating the involvement of additional biological or biochemical changes in viral entry. The developed mathematical model offers potential for the mechanobiological assessment of the invagination of enveloped viruses towards improving the prevention and treatment of viral infections.

biophysics↗

bioRxiv2019

In silico stress fibre content affects peak strain in cytoplasm and nucleus but not in membrane for uniaxial substrate stretch

Existing in silico models for single cell mechanics feature limited representations of cytoskeletal structures that contribute substantially to the mechanics of a cell. We propose a micromechanical hierarchical approach to capture the mechanical contribution of actin stress fibres. For a cell-specific fibroblast geometry with membrane, cytoplasm and nucleus, the Mori-Tanaka homogenization method was employed to describe cytoplasmic inhomogeneities and constitutive contribution of actin stress fibres. The homogenization was implemented in a finite element model of the fibroblast attached to a substrate through focal adhesions. Strain in cell membrane, cytoplasm and nucleus due to uniaxial substrate stretch was assessed for different stress fibre volume fractions and different elastic modulus of the substrate. A considerable decrease of the peak strain with increasing stress fibre content was observed in cytoplasm and nucleus but not the membrane, whereas the peak strain in cytoplasm, nucleus and membrane increased for increasing elastic modulus of the substrate.

biophysics↗