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Giunta, G.

Publications and source records attributed to Giunta, G..

3 recordsLinked to original sources

Force Generation by Enhanced Diffusion in Enzyme-Loaded Vesicles

Recent experiments have shown that the diffusion coefficient of some metabolic enzymes increases with the concentration of their cognate substrate, a phenomenon known as enhanced diffusion. In the presence of substrate gradients, enhanced diffusion induces enzymatic drift, resulting in a non-homogeneous enzyme distribution. Here, we study the effects of enhanced diffusion on enzyme-loaded vesicles placed in external substrate gradients using a combination of computer simulations and analytical modeling. We observe that the spatially inhomogeneous enzyme profiles generated by enhanced diffusion result in a pressure gradient across the vesicle, which leads to macroscopically observable effects, such as deformation and self-propulsion of the vesicle. Our analytical model allows us to characterize dependence of the velocity of propulsion on experimentally tunable parameters. The effects predicted by our work provide an avenue for further validation of enhanced diffusion, and might be leveraged for the design of novel synthetic cargo transporters, such as targeted drug delivery systems.

biophysics↗

Empirical modeling of a single polymer collapsing under the entropic pressure of neutral crowders

Macromolecular crowding can induce the collapse of a single long polymer into a globular form due to depletion forces of entropic nature. This phenomenon has been shown to play a significant role in compacting the genome within the bacterium Escherichia coli into a well-defined region of the cell known as the nucleoid. Motivated by the biological significance of this process, numerous theoretical and computational studies have searched for the primary determinants of the behavior of polymer-crowder phases. However, our understanding of this process remains incomplete and there is debate on a quantitatively unified description. In particular, different simulation studies with explicit crowders have proposed different order parameters as potential predictors for the collapse transition. In this work, we present a comprehensive analysis of published simulation data obtained from different sources. Based on the common behavior we find in this data, we develop a unified phenomenological model that we show to be predictive. Finally, to further validate the accuracy of the model, we conduct new simulations on polymers of various sizes, and investigate the role of jamming of the crowders.

biophysics↗

Optimal spatial allocation of enzymes as an investment problem

Given a limited number of molecular components, cells face various allocation problems demanding decisions on how to distribute their resources. For instance, cells decide which enzymes to produce at what quantity, but also where to position them. Here we focus on the spatial allocation problem of how to distribute enzymes such as to maximize the total reaction flux produced by them in a system with given geometry and boundary conditions. So far, such distributions have been studied by computational optimization, but a deeper theoretical understanding was lacking. We derive an optimal allocation principle, which demands that the available enzymes are distributed such that the marginal flux returns at each occupied position are equal. This homogeneous marginal returns criterion (HMR criterion) corresponds to a portfolio optimization criterion in a scenario where each investment globally feeds back onto all payoffs. The HMR criterion allows us to analytically understand and characterize a localization-delocalization transition in the optimal enzyme distribution that was previously observed numerically. In particular, our analysis reveals the generality of the transition, and produces a practical test for the optimality of enzyme localization by comparing the reaction flux to the influx of substrate. Based on these results, we devise an additive construction algorithm, which builds up optimal enzyme arrangements systematically rather than by trial and error. Taken together, our results reveal a common principle in allocation problems from biology and economics, which can also serve as a design principle for synthetic biomolecular systems.

bioengineering↗