Adapt locally and act globally: strategy to maintain high chemoreceptor sensitivity in complex environments

In bacterial chemotaxis, several types of receptors form mixed clusters. Receptor adaptation is shown to depend on the receptor's own conformational state rather than on the cluster's global activity, enabling cells to differentiate stimuli in complex environments

Mechanochemical regulation of oscillatory follicle cell dynamics in the developing Drosophila egg chamber

During tissue elongation from stage 9 to stage 10 in Drosophila oogenesis, the egg chamber increases in length by ∼1.7-fold while increasing in volume by eightfold. During these stages, spontaneous oscillations in the contraction of cell basal surfaces develop in a subset of follicle cells. This patterned activity is required for elongation of the egg chamber; however, the mechanisms generating the spatiotemporal pattern have been unclear. Here we use a combination of quantitative modeling and experimental perturbation to show that mechanochemical interactions are sufficient to generate oscillations of myosin contractile activity in the observed spatiotemporal pattern. We propose that follicle cells in the epithelial layer contract against pressure in the expanding egg chamber. As tension in the epithelial layer increases, Rho kinase signaling activates myosin assembly and contraction. The activation process is cooperative, leading to a limit cycle in the myosin dynamics. Our model produces asynchronous oscillations in follicle cell area and myosin content, consistent with experimental observations. In addition, we test the prediction that removal of the basal lamina will increase the average oscillation period. The model demonstrates that in principle, mechanochemical interactions are sufficient to drive patterning and morphogenesis, independent of patterned gene expression

A treatise on theoretical and computational mechanobiology in myosin motors and bacterial cell division

This dissertation focuses on theoretical and computational study of several mechanobiological systems, including myosin motors and bacterial cells. The techniques applied in this study are mainly from elasticity theory and statistical mechanics, but need to be further developed to be applicable. To this end, we first comprehensively analyze myosin processivity and prokaryotic cytokinesis, and then propose new treatments for those complex problems based on a mechanobiological point of view. For the myosin motor system, we propose that conformations of the motor control its ATPase activity, and the probability for the motor to be in various conformations is determined by the structural deformation energy. Treating myosin as a combination of several elastic elements, we compute the deformation energy and adjust motor kinetics accordingly. This treatment successfully explained the processivity of myosin-V and VI. Furthermore, the same framework can be applied to the sarcomere, an ordered array of myosin motors in muscle, by coupling ∼150 myosin motors together. A molecular explanation of skeleton muscle physiological performance is revealed. Our model suggests and confirms that mechanical energy regulates single myosin motor behavior, and the regulated motor kinetics together with the mechanical coupling in muscle structure synchronize the myosin array. For bacterial cells, we are interested in FtsZ ring driven cell division. We first explore the morphological process during bacterial cell division, and develop a mathematical theory for self-modifying cylindrical shell with anisotropic elastic properties. We quantitatively evaluate contributions from mechanical and biochemical factors during division and conclude that biochemical activity of the cell wall is the dominant contributor. Cell shapes and division velocities are computed. We study the FtsZ ring contraction and force generation. A kinetic model that includes fragmentable single- and double-strand FtsZ filaments is developed to explain in vitro FtsZ polymerization. FtsZ protein self-interaction energies are computed and used to construct a lattice model for in vivo FtsZ division ring formation and contraction. We calculate the force during division and show that lateral interaction induced FtsZ condensation is the origin of force generation

Dynamics of Myosin-V Processivity

Myosin-V is an actin-associated processive molecular motor. Single molecule experiments revealed that myosin-V walks in a stepwise fashion with occasional backward steps. By combining the mechanical structure of the motor with the ATP hydrolysis kinetics, we construct a dynamical model that accounts for the stepwise processivity. The molecular properties of the protein chains connecting the myosin heads are important. A simple elastic model demonstrates that the stress transmitted from the leading head to the trailing head leads to net forward motion. The step-sizes are non-uniform. We also predict there are several substeps. The translational speed and step-size distributions are computed for several different conditions. The computed force-versus-velocity curve shows that under an external load, myosin-V slows down. However, the sizes of the steps remain the same

Dissipated free energy (A) and the number of cytoplasmic MinE (B) as functions of <i>γ</i> by changing <i>k</i>₋₁.

<p>The inset shows the same dissipation free energy, but in logarithmic scale. Oscillation occurs when <i>γ</i> > 2.8 × 10⁶ (circles). The dissipation rate is very close to the theoretical limit obtained from kinetic analysis (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004351#pcbi.1004351.e010" target="_blank">Eq (3)</a>, red dashed line) in the oscillatory regime where almost all the MinE dimers are bound on the membrane. Parameters used in the simulation are: <i>k</i>₋₂ = 0.01 <i>s</i>⁻¹, <math><mrow><msubsup><mi>k</mi><mrow><mo>−</mo><mn>2</mn></mrow><mo>′</mo></msubsup><mo>=</mo><mn>0</mn><mo>.</mo><mn>001</mn><mo></mo><mi>μ</mi><mi>m</mi><mn>2</mn><mi>s</mi><mrow><mo>−</mo><mn>1</mn></mrow></mrow></math>, <i>k</i>₋₃ = 0.04 <i>s</i>⁻¹ and <i>k</i>₋₄ = 10⁻⁵<i>μm</i>⁴<i>s</i>⁻¹. Other parameters are given in the main text.</p

An Optimal Free Energy Dissipation Strategy of the MinCDE Oscillator in Regulating Symmetric Bacterial Cell Division

<div><p>Sustained molecular oscillations are ubiquitous in biology. The obtained oscillatory patterns provide vital functions as timekeepers, pacemakers and spacemarkers. Models based on control theory have been introduced to explain how specific oscillatory behaviors stem from protein interaction feedbacks, whereas the energy dissipation through the oscillating processes and its role in the regulatory function remain unexplored. Here we developed a general framework to assess an oscillator’s regulation performance at different dissipation levels. Using the <i>Escherichia coli</i> MinCDE oscillator as a model system, we showed that a sufficient amount of energy dissipation is needed to switch on the oscillation, which is tightly coupled to the system’s regulatory performance. Once the dissipation level is beyond this threshold, unlike stationary regulators’ monotonic performance-to-cost relation, excess dissipation at certain steps in the oscillating process damages the oscillator’s regulatory performance. We further discovered that the chemical free energy from ATP hydrolysis has to be strategically assigned to the MinE-aided MinD release and the MinD immobilization steps for optimal performance, and a higher energy budget improves the robustness of the oscillator. These results unfold a novel mode by which living systems trade energy for regulatory function.</p></div