Welcome to the Gerland group -
Physics of Complex Biosystem
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
Establishing sharp and correctly positioned boundaries in spatial gene expression patterns is a central task in both developmental and synthetic biology. We consider situations where a global morphogen gradient provides positional information to cells but is insufficient to ensure the required boundary precision, due to different types of noise in the system. In a conceptual model, we quantitatively compare three mechanisms, which combine the global signal with local signaling between neighboring cells, to enhance the boundary formation process. These mechanisms differ with respect to the way in which they combine the signals by following either an AND, an OR, or a SUM rule. Within our model, we analyze the dynamics of the boundary formation process, and the fuzziness of the resulting boundary. Furthermore, we consider the tunability of the boundary position and its scaling with system size. We find that all three mechanisms produce less fuzzy boundaries than the purely gradient-based reference mechanism, even in the regime of high noise in the local signals relative to the noise in the global signal. Among the three mechanisms, the SUM rule produces the most accurate boundary. However, in contrast to the other two mechanisms, it requires noise to exit metastable states and rapidly reach the stable boundary pattern.
Suspended microparticles subjected to ac electrical fields collectively organize into band patterns perpendicular to the field direction. The bands further develop into zigzag shaped patterns, in which the particles are observed to circulate. We demonstrate that this phenomenon can be observed quite generically by generating such patterns with a wide range of particles: silica spheres, fatty acid, oil, and coacervate droplets, bacteria, and ground coffee. We show that the phenomenon can be well understood in terms of second order electrokinetic flow, which correctly predicts the hydrodynamic interactions required for the pattern formation process. Brownian particle simulations based on these interactions accurately recapitulate all of the observed pattern formation and symmetry-breaking events, starting from a homogeneous particle suspension. The emergence of the formed patterns can be predicted quantitatively within a parameter-free theory.
Catalytic particles are spatially organized in a number of biological systems across different length scales, from enzyme complexes to metabolically coupled cells. Despite operating on different scales, these systems all feature localized reactions involving partially hindered diffusive transport, which is determined by the collective arrangement of the catalysts. Yet it remains largely unexplored how different arrangements affect the interplay between the reaction and transport dynamics, which ultimately determines the flux through the reaction pathway. Here we show that two fundamental trade-offs arise, the first between efficient inter-catalyst transport and the depletion of substrate, and the second between steric confinement of intermediate products and the accessibility of catalysts to substrate. We use a model reaction pathway to characterize the general design principles for the arrangement of catalysts that emerge from the interplay of these trade-offs. We find that the question of optimal catalyst arrangements generalizes the well-known Thomson problem of electrostatics.
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