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Peterson, M. S.

Publications and source records attributed to Peterson, M. S..

2 recordsLinked to original sources

Active membrane deformations of a minimal synthetic cell

Biological cells exhibit the remarkable ability to adapt their shape in response to their environment, a phenomenon that hinges on the intricate interplay between their deformable membrane and the underlying activity of their cytoskeleton. Yet, the precise physical mechanisms of this coupling remain mostly elusive. Here, we introduce a synthetic cell model, comprised of an active cytoskeletal network of microtubules, crosslinkers and molecular motors encapsulated inside giant vesicles. Remarkably, these active vesicles exhibit large shape fluctuations and life-like morphing abilities. Active forces from the encapsulated cytoskeleton give rise to large-scale traveling membrane deformations. Quantitative analysis of membrane and microtubule fluctuations shows how the intricate coupling of confinement, membrane material properties and cytoskeletal forces yields fluctuation spectra whose characteristic scales in space and time are distinctly different from passive vesicles. We demonstrate how activity leads to uneven probability fluxes between fluctuation modes and hence sets the temporal scale of membrane fluctuations. Using simulations and theoretical modelling, we extend the classical approach to membrane fluctuations to active cytoskeleton-driven vesicles, highlighting the effect of correlated activity on the dynamics of membrane deformations and paving the way for quantitative descriptions of the shape-morphing ability typical of living systems.

biophysics↗

Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi

BackgroundKra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype. MethodsKra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections. ResultsAs expected, the kra monkeys controlled parasitaemia and remained with low-level, persistent parasitaemias without antimalarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopaenia, and moderate to severe anaemia. Mathematical modeling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low. ConclusionsKra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3-5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.

pathology↗