Local changes in pH are known to significantly alter the state and activity of proteins and in particular enzymes. pH variations induced by pulses propagating along soft interfaces (e.g. the lipid bilayer) would therefore constitute an important pillar towards a new physical mechanism of biochemical regulation and biological signaling. Here we investigate the pH-induced physical perturbation of a lipid interface and the physiochemical nature of the subsequent acoustic propagation. Pulses are stimulated by local acidification of a lipid monolayer and propagate, in analogy to sound, at velocities controlled by the two-dimensional compressibility of the interface. With transient local pH changes of 0.6 units directly observed at the interface and velocities up to 1.4 m/s this represents hitherto the fastest protonic communication observed. Furthermore simultaneously propagating mechanical and electrical changes in the lipid interface up to 8 mN/m and 100 mV are detected, exposing the thermodynamic nature of these pulses. Finally, these pulses are excitable only beyond a threshold for protonation, determined by the pKa of the lipid head groups. When combined with an enzymatic pH-optimum, the proposed communication can be very specific, thus providing a new physical basis for intra- and intercellular signaling via two-dimensional sound waves at interfaces.
Biological signaling is imagined as a combination of activation and transport. The former is triggered by local molecular interactions and the latter is the result of molecular diffusion. However, other fundamental physical principles of communication have yet to be addressed. We have recently shown, that lipid interfaces allow for the excitation and propagation of sound pulses. Here we demonstrate, that these reversible perturbations can control the activity of membrane embedded enzymes without the necessity of molecular transport. They therefore allow for the rapid communication between dist…
Currently, biological signaling is envisaged as a combination of activation and movement, triggered by local molecular interactions and molecular diffusion, respectively. However, we here suggest, that other fundamental physical mechanisms might play an at least equally important role. We have recently shown that lipid interfaces permit the excitation and propagation of sound pulses. Here we demonstrate that these reversible perturbations can control the activity of membrane-embedded enzymes without a requirement for molecular transport. They can thus facilitate rapid communication between dis…
In 2005, we proposed that the nerve pulse is an electromechanical soliton. This concept represents a challenge to the well-known Hodgkin-Huxley model which is of a purely electrical nature. The soliton theory was criticized by Nimtz and Aichmann in a recent article in Zeitung für Naturforschung A. Here, we wish to comment on some statements that we regard as misinterpretations of our views.
Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switch-like properties which are critical to their biological functi…
Information transmission in biological signaling circuits has often been described using the metaphor of a noise filter. Cellular systems need accurate, real-time data about their environmental conditions, but the biochemical reaction networks that propagate, amplify, and process signals work with noisy representations of that data. Biology must implement strategies that not only filter the noise, but also predict the current state of the environment based on information delayed due to the finite speed of chemical signaling. The idea of a biochemical noise filter is actually more than just a m…
Mechanical algesia is an important process for the preservation of living organisms, allowing potentially life-saving reflexes or decisions when given body parts are stressed. Yet, its various underlying mechanisms remain to be fully unravelled. Here, we quantitatively discuss how the detection of painful mechanical stimuli by the human central nervous system may, partly, rely on thermal measurements. Indeed, most fractures in a body, including microscopic ones, release some heat, which diffuses in the surrounding tissues. Through this physical process, the thermo-sensitive TRP proteins, that …
Thermogenesis is a physiological activity of releasing heat that originates from intracellular biochemical reactions. Recent experimental studies discovered that externally applied heat changes intracellular signaling locally, resulting in global changes in cell morphology and signaling. Therefore, we hypothesize an inevitable contribution of thermogenesis in modulating biological system functions throughout the spatial scales from molecules to individual organisms. One key issue examining the hypothesis, namely, the "trans-scale thermal signaling," resides at the molecular scale on the amount…
In systems biology effective models are widely used due to the complexity of biological system. They result from a coarse-graining process which employs specific assumptions. Frequently one does not start with a model taking all details into account and then performs a coarse-graining process, but rather one starts right away with the effective equations and often the underlying assumptions remain hidden or unclear. We exemplify the analysis of an effective model by analyzing a time delay equation for the JAK/STAT5 signaling pathway and show how one can avoid wrong conclusions and obtain a dee…
Signal transduction is an important and basic mechanism to cell life activities. The stochastic state transition of receptor induces the release of signaling molecular, which triggers the state transition of other receptors. It constructs a nonlinear sigaling network, and leads to robust switchlike properties which are critical to biological function. Network architectures and state transitions of receptor affect the performance of this biological network. In this work, we perform a study of nonlinear signaling on biological polymorphic network by analyzing network dynamics of the Ca$^{2+}$ in…
To deal with permanent deformations and residual stresses, we consider a morphoelastic model for the scar formation as the result of wound healing after a skin trauma. Next to the mechanical components such as strain and displacements, the model accounts for biological constituents such as the concentration of signaling molecules, the cellular densities of fibroblasts and myofibroblasts, and the density of collagen. Here we present stability constraints for the one-dimensional counterpart of this morphoelastic model, for both the continuous and (semi-) discrete problem. We show that the trunca…
Nonlinear systems driven by recurrent signals are known to exhibit complex dynamical responses which, in the physiological context, can have important functional consequences. One of the simplest biological systems that is exposed to such repeated stimuli is the intra-cellular signaling network. In this paper we investigate the periodic activation of an evolutionarily conserved motif of this network, viz., the mitogen-activated protein kinase (MAPK) signaling cascade, with a train of pulses. The resulting response of the cascade, which shows integrative capability over several successive pulse…
Lipid rafts are heterogeneous dynamic lipid domains of the cell membranes that are involved in several biological processes, like protein and lipids specific transport and signaling. Our understanding of lipid raft formation is still limited, due to the transient and elusive nature of these domains {\it in vivo}, in contrast to the stable phase-separated domains observed in artificial membranes. Inspired by experimental findings highlighting the relevance of transmembrane proteins for lipid rafts, we investigate lipid domain nucleation by coarse-grained molecular dynamics and Ising model simul…
Maximizing the speed and precision of communication while minimizing power dissipation is a fundamental engineering design goal. Also, biological systems achieve remarkable speed, precision and power efficiency using poorly understood physical design principles. Powerful theories like information theory and thermodynamics do not provide general limits on power, precision and speed. Here we go beyond these classical theories to prove that the product of precision and speed is universally bounded by power dissipation in any physical communication channel whose dynamics is faster than that of the…
