Background The protective efficacy of the most promising malaria whole-parasite based vaccine candidates critically depends on the parasite’s potential to migrate in the human host. Key components of the parasite motility machinery (e.g. adhesive proteins, actin/myosin-based motor, geometrical properties) have been identified, however the regulation of this machinery is an unknown process. Methods In vitro microscopic live imaging of parasites in different formulations was performed and analysed, with the quantitative analysis software SMOOT In vitro , their motility; their adherence capacity, movement pattern and velocity during forward locomotion. Results SMOOT In vitro enabled the detailed analysis of the regulation of the motility machinery of Plasmodium berghei in response to specific (macro)molecules in the formulation. Albumin acted as an essential supplement to induce parasite attachment and movement. Glucose, salts and other whole serum components further increased the attachment rate and regulated the velocity of the movement. Conclusions Based on the findings can be concluded that a complex interplay of albumin, glucose and certain salts and amino acids regulates parasite motility. Insights in parasite motility regulation by supplements in solution potentially provide a way to optimize the whole-parasite malaria vaccine formulation. Electronic supplementary material The online version of this article (10.1186/s12936-019-2794-y) contains supplementary material, which is available to authorized users.
Many biological materials consist of sparse networks of disordered fibres, embedded in a soft elastic matrix. The interplay between rigid and soft elements in such composite networks leads to mechanical properties that can go far beyond the sum of those of the constituents. Here we present lattice-based simulations to unravel the microscopic origins of this mechanical synergy. We show that the competition between fibre stretching and bending and elastic deformations of the matrix gives rise to distinct mechanical regimes, with phase transitions between them that are characterized by critical behaviour and diverging strain fluctuations and with different mechanisms leading to mechanical enhancement. Many materials, ranging from textiles and paper to connective tissue and the cytoskeleton of living cells, have a microscopic structure that consists of crosslinked fibres. Theoretical progress in the last decades has led to a detailed understanding of the physics of such fibre networks [1]. Because stiff fibres resist not only stretching, but also bending, the mechanical behaviour of fibre networks differs significantly from that of networks of flexible polymers. Different mechanical regimes can be observed: at high densities fibre networks deform affinely and the elasticity is governed by fibre stretching, while at lower densities there is a crossover to a non-affine, bending-dominated regime [2][3][4][5][6].Although experiments on model networks give support to the existence of different mechanical regimes [7][8][9], the current theories fall short in describing real biomaterials. An important reason for this is that natural materials are almost without exception composite materials that consist of mixtures of elements of different rigidity: the cytoskeleton is a complex network of (partially bundled) actin filaments, intermediate filaments, and microtubules [10]; the extracellular matrix consists of stiff collagen fibres in a matrix of more flexible polymers [11]; and also many synthetic high-performance materials are composites of soft and rigid fibres [12][13][14][15][16]. It is clear that the collective non-affine deformation modes that characterize the mechanics of sparse fibre networks must be hindered significantly by the presence of an elastic matrix [17][18][19][20][21], but a fundamental understanding of how this interplay affects the mechanical properties of composites has remained elusive.Here we use numerical simulations to study the mechanics of disordered composite networks, consisting of crosslinked fibres embedded in a soft elastic matrix. Both the fibres and the polymers that constitute the background matrix are arranged on a 2D triangular lattice with lattice spacing l 0 , as shown in Fig. 1. The effects of connectivity are explored by randomly removing segments of the fibre network with a probability 1 − p, so that the average connectivity equals z = 6p. Sequences of contiguous colinear fibre segments are treated as elastic rods, characterized by a stretch modulus µ 1 and a bending modulus κ 1 ....
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