Welcome to the Gerland group -
Physics of Complex Biosystem
Vision
In physics, interactions between particles follow laws. In biology, interactions between biomolecules serve a function. These very different points of view are beginning to merge as research over the past years has demonstrated how, in some exemplary cases, the laws of physics constrain the implementation of biological function.
We investigate several such cases. For instance, we study how the spatial arrangement and coordination of enzymes determines the efficiency of a multi-step reaction. These spatial arrangements can be natural (as in biomolecular complexes) or engineered with the modern methods of bio-nanotechnology. In both cases, fundamental functional tradeoffs emerge, which must be characterized to understand the optimization of such systems.
Methods from theoretical physics help to describe the functioning of these complex biomolecular systems on a quantitative level, while the biological function leads to new questions, with many parallels in the engineering disciplines. Seen from this perspective, a bacterium is a microscopic bioreactor programmed by evolution to rebuild itself from a variable set of resources and in fluctuating environments. How is this bioreactor programmed? Which strategies enable the control of a diverse set of physico-chemical processes in a way as to robustly produce a highly complex product? Quantitative analysis and modeling facilitates insight into the underlying design principles.
Recent Research Highlights
A quantitative framework for bacterial competition during starvation
Bacterial communities are inherently characterized by recurring cycles of feast and famine, which creates distinct forms of competition when cells compete for recycled necromass. In this work, we develop a quantitative framework for the competition of isogenic Escherichia coli populations whose starvation physiology is tuned by prior growth history. If starved individually, fast-grown populations have higher maintenance demands and die slightly faster, while slow-grown populations are better adapted to starvation, leading to a slower decline in cell density. However, when mixing both populations, these differences are exaggerated in a frequency-dependent manner: Populations with high maintenance demand die several-fold faster than in monoculture, whereas better adapted populations reduce their death rate below that of stationary-phase adapted monocultures. Our framework shows that survival in competition is governed by a self-amplifying necromass recycling feedback, in which the majority population sets the shared energy pool, constituted by released biomass from dead cells. This shows that phenotypic differences alone are sufficient to predict selection under starvation, and our framework provides a mechanistic and predictive basis as a starting point for modelling multi-species environments such as biofilms or trade-off scenarios between rapid growth and long-term survival.
Pressure-induced Shape-shifting of Helical Bacteria

Many bacterial species are helical in form, including the widespread pathogen Helicobacter pylori. Motivated by recent experiments on H. pylori showing that cell wall synthesis is not uniform, we investigate the possible formation of helical cell shape induced by elastic heterogeneity. We show, experimentally and theoretically, that helical morphogenesis can be produced by pressurizing an elastic cylindrical vessel with helical reinforced lines. The properties of the pressurized helix are highly dependent on the initial helical angle of the reinforced region. We find that steep angles result in crooked helices with, surprisingly, reduced end-to-end distance upon pressurization. This work helps to explain the possible mechanisms for the generation of helical cell morphologies and may inspire the design of novel pressure-controlled helical actuators
Formation mechanism of thermally controlled pH gradients

Spatial proton gradients create energy in biological systems and are likely a driving force for prebiotic systems. Due to the fast diffusion of protons, they are however difficult to create as steady state, unless driven by other non-equilibria such as thermal gradients. Here, we quantitatively predict the heat-flux driven formation of pH gradients for the case of a simple acid-base reaction system. To this end, we (i) establish a theoretical framework that describes the spatial interplay of chemical reactions with thermal convection, thermophoresis, and electrostatic forces by a separation of timescales, and (ii) report quantitative measurements in a purpose-built microfluidic device. We show experimentally that the slope of such pH gradients undergoes pronounced amplitude changes in a concentration-dependent manner and can even be inverted. The predictions of the theoretical framework fully reflect these features and establish an understanding of how naturally occurring non-equilibrium environmental conditions can drive pH gradients.
Optimal spatial allocation of enzymes as an investment problem

Cells face various allocation problems demanding decisions on how to distribute their finite resources. They decide which enzymes to produce at what quantity, but also where to position them. Here we focus on the spatial allocation problem of arranging enzymes such as to maximize the total reaction flux produced by them in a system with given geometry and boundary conditions. We derive an optimal allocation principle demanding that the available enzymes are distributed such that the marginal flux returns at each occupied position are equal. This ‘homogeneous marginal returns’ (HMR) criterion corresponds to a portfolio optimization of investments that globally feed back onto all payoffs. The HMR criterion allows us to analytically understand and characterize a localization-delocalization transition in the optimal enzyme distribution. Our analysis reveals the generality of the transition, and produces a practical test for the optimality of enzyme clustering by comparing the reaction flux to the influx of substrate. Based on these results, we devise an additive construction scheme, which builds up optimal enzyme arrangements systematically rather than by trial and error. Taken together, we identify a common principle in allocation problems from biology and economics, which also serves as a design principle for synthetic biomolecular systems.
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