Fluctuations and Nonequilibrium Systems
On a molecular and cellular level all living systems display two fundamental features: first, they transduce energy to maintain a nonequilibrium state and second they operate on the scale of thermal fluctuations at which the stochastic interactions of molecules have important implications. Although we mainly use theoretical approaches, we connect our results to experimental results whenever it is possible. We believe that the mutual stimulation of theoretical considerations and experimental findings is a beautiful way to decipher nature's principles.
Stochastic nonlinear dynamics: time series analysis of the duffing oscillator
The most interesting and complex behavior in nature arises from coupled systems with nonlinearities embedded in an environment. Depending on the relevant time and length scales influences from the environment are often considered as effective driving forces or simply fluctuations. In this study, Roman Belousov developed a detailed Volterra-series approach to determine from time series of a Duffing oscillator the underlying parameters. This is a promising new way to study random dynamical systems that we plan to apply to the stochastic oscillations of hair bundles.
Force-dependent unbinding rate of molecular motors
Molecular motors unbind from their filaments stochastically with a force-dependent unbinding rate. The precise functional form how the unbinding rate depends on the force is a crucial quantitiy to understand motor behavior and their responds to external forces. In this study we show that this force-dependent unbinding rate can be obtained from the analysis of experimental data of a molecular motor moving in a stationary optical trap. In a stationary trap the force on the motor is increasing while it pulls the bead away from the trap center. We present two complementary approaches to analyse such data and obtain the force-dependent unbinding rate for kinesin-1.
Tau regulates bidirectional transport
We studied the regulation of bidirectional transport of phagosomes. These vesicles are transported along microtubles by kinesin-1, kinesin-2, and dynein motors. Combining in vitro reconstitution, optical trapping and mathematical modeling, we showed that the microtubule associated protein tau mostly inhibits kinesin-1 motility resulting in a non-trivial change of the bidirectional transport and the force production. The experiments were carried out by Abdullah Chaudhary in Adam Hendricks' lab and I contributed the mathematical model for the data analysis.
Chemomechanical regulation of myosin Ic cross-bridges
A hallmark of biological sensory systems is adaptation: the ability to retain sensitivity during a prolonged stimulus. In the inner ear, where a mechanical stimulus is transduced into an electrical signal, myosin Ic molecules regulate the tension on tension-gated ion channels and thus form the molecular bases for adaptation. We introduced a thermodynamically consistent enzymatic cycle description for myosin Ic and showed that a calcium induced change of its stiffness could account for the fast phase of adaptation, as seen in physiological experiments. This study combines numerical values for the transition rates from different biochemical experiments into a single cycle description for myosin Ic.