Santos, A. L. | Search bioRxiv

bioRxiv2022

Molecular machines stimulate intercellular calcium waves and cause muscle contraction

Intercellular calcium waves (ICW) are complex signaling phenomena that control many essential biological activities, including smooth muscle contraction, vesicle secretion, gene expression, and changes in neuronal excitability. Accordingly, the remote stimulation of ICW may result in versatile new biomodulation and therapeutic strategies. Here, we demonstrate that light-activated molecular machines (MM), molecules that rotate and perform mechanical work on the molecular scale, can remotely stimulate ICW. Live-cell calcium tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol triphosphate (IP3) mediated signaling pathways by unidirectional, fast-rotating MM. We then demonstrated that MM-induced ICW can be used to control muscle contraction in vitro in cardiomyocytes and animal behavior in vivo in Hydra vulgaris. Consequentially, this work demonstrates a new strategy for the direct control of cell signaling and downstream biological function using molecular-scale devices.

bioengineering↗

bioRxiv2018

Temporal scaling of ageing as an adaptive strategy of Escherichia coli

Natural selection has long been hypothesised to shape ageing patterns, but whether and how ageing contributes to life-history evolution remains elusive. The complexity of various ageing-associated molecular mechanisms and their inherent stochasticity hinder reductionist approaches to the understanding of functional senescence, i.e. reduced fecundity and increased mortality. Recent bio-demographic work demonstrated that high-precision statistics of life-history traits such as mortality rates could be used phenomenologically to understand the ageing process. We adopted this approach to study cellular senescence in growth-arrested E. coli cells, where damages to functional macromolecules are no longer diluted by fast de novo biosynthesis. We acquired high-quality longitudinal physiological and life history data of large environmentally controlled clonal E. coli populations at single-cell resolution, using custom-designed microfluidic devices coupled to time-lapse microscopy. We show that E. coli lifespan distributions follow the Gompertz law of mortality, a century-old actuarial observation of human populations, despite developmental, cellular and genetic differences between bacteria and metazoan organisms. Measuring the shape of the hazard functions allowed us to disentangle quantitatively the demographic effects of ageing, which accumulate with time, from age-independent genetic longevity-modulating interventions. A pathway controlling cellular maintenance, the general stress response, not only promotes longevity but also temporally scales the whole distribution by reducing ageing rate. We further show that E. coli, constrained by the amount of total biosynthesis, adapt to their natural feast-or-famine lifestyle by modulating the amount of maintenance investment, rendering ageing rate a highly evolvable life-history trait.

evolutionary biology↗