Erythrocyte’s aging in microgravity highlights how environmental stimuli shape metabolism and morphology

Abstract

The determination of the function of cells in zero-gravity conditions is a subject of interest in many different research fields. Due to their metabolic unicity, the characterization of the behaviour of erythrocytes maintained in prolonged microgravity conditions is of particular importance. Here, we used a 3D-clinostat to assess the microgravity-induced modifications of the structure and function of these cells, by investigating how they translate these peculiar mechanical stimuli into modifications, with potential clinical interest, of the biochemical pathways and the aging processes. We compared the erythrocyte’s structural parameters and selected metabolic indicators that are characteristic of the aging in microgravity and standard static incubation conditions. The results suggest that, at first, human erythrocytes react to external stimuli by adapting their metabolic patterns and the rate of consumption of the cell resources. On longer timeframes, the cells translate even small differences in the environment mechanical solicitations into structural and morphologic features, leading to distinctive morphological patterns of aging.

Effects of sedimentation, microgravity, hydrodynamic mixing and air–water interface on α-synuclein amyloid formation

“…The protein solution was studied in three different dynamic conditions: (1) static; (2) orbital shaking, achieved by shaking at 400 rpm (rotations per minute) on a circular orbit on the horizontal plane; (3) microgravity environment, implemented by using a random position machine (RPM) with a 3Dlinostat conguration, rotating at $30 rpm. 29,39 Additionally, for each dynamic condition, the protein solution was sealed and incubated either in an Eppendorf tube in the presence of an airwater interface or in a syringe in the absence of any air-water interface. The experiments were performed at pH 7.4, at 37 C and at a variable initial monomeric concentration between 20 and 65 mM.…”

“…The microgravity environment was simulated by using a self-build random position machine (RPM) with the reported protocol. 29 This RPM system was realized by employing 3D-clinostat conguration [53][54][55] to rotate three-dimensionally the sample with well-controlled speed and acceleration. This RPM system contains two independent high-precision motors to give a random rotation orientation and gravity vector on the sample, providing a simulated microgravity condition for protein aggregation.…”

“…9,17,19 The poorly controlled presence of hydrophobic interfaces can cause uncertainty and variability in the kinetics of aggregation, as well as a high degree of polymorphism. 19,[21][22][23][24][25] Furthermore, many biological activities are gravity-dependent, 26 such as lipid membrane uidity [27][28][29] and ion channels, 30 and it has been reported that microgravity and hyper-gravity conditions with under/over-sedimentation effect can promote or hinder the aggregation process respectively. 31 However the gravitational inuence on protein aggregation is still not fully understood 31,32 and the understanding of the combined phenomena of sedimentation, hydrodynamic mixing and interaction with air-water interfaces on protein aggregation remains elusive.…”

Insights into the morphological pattern of erythrocytes' aging: Coupling quantitative AFM data to microcalorimetry and Raman spectroscopy

“…In particular, it is often assumed that this cellular structure is the key factor that determines the cell shape. The cytoskeletal structure and dynamics are influenced by environmental effectors and by the specific biochemical/energetic status of the cell, in such a way that transient or permanent shape alterations can occur. Given the link between the cell's shape, its biochemical status, and the environmental conditions, we have chosen to analyse how these cellular parameters vary along the ageing process of our samples.…”

The Erythrocytic Hypothesis of Brain Energy Crisis in Sporadic Alzheimer Disease: Possible Consequences and Supporting Evidence

“…For instance, in AD patients RBCs have been found to exhibit morphological changes [46,47], leading to decreased deformability [48], perturbations in the physical state of membrane proteins [49,50], and oxidant/antioxidant equilibrium [51][52][53][54]. These changes are in some way due to the destabilization of intracellular metabolism in erythrocytes [55][56][57][58]. However, the mechanisms underlying the foregoing alterations in RBC metabolism in AD patients are not fully understood.…”