Commentary and Perspective
Hybrid Biophysics: Interdisciplinary approaches for trans-scale analysis of organism-environment interactions
2023 Volume 20 Issue 4 Article ID: e200043
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2023 Volume 20 Issue 4 Article ID: e200043
Interaction of an organism with its external environment is observed over a wide range of spatial scales in the hierarchy of a biological system, from the biomolecular, to the cellular, and to the organismal scale. The first step of the interaction is the sensing of internal and external stimuli. Mechano-, thermo- and light-sensing ion channels are the representative sensor biomolecules that manage the cellular sensing of force, heat and photons, respectively. The information from the sensors is transmitted into the cell via various types of signaling modes, such as Ca2+ and phosphorylation. Heat itself can also be a signaling, i.e., the thermal signaling [1–3]. Cellular responses are transduced and coordinated at the organismal level to determine behavior. At the organismal level, individual organisms communicate with each other through, for example, colors, voices and body movements. To comprehensively understand the organism-environment interactions, trans-scale analysis from molecules to organism is desired in addition to those at each level.
The trans-scale analysis cannot be achieved by a single conventional approach due to the limitations of scale transfer. For example, the development of a novel fluorescence microscopy is closely linked to the engineering of biological and chemical fluorescent molecules. Optical microscopy is suitable for biomolecular and cellular analysis but is not for revealing the atomic coordinates. In atomic simulations, increasing the spatial and temporal scales to the cellular level currently requires an unrealistically large computational cost. Thus, there is a need to combine different expertise; i.e., hybrid interdisciplinary approaches are required for the trans-scale analysis.
The symposium entitled “Interdisciplinary approaches for trans-scale analysis of organism-environment interactions” at the 61th Annual Meeting of the Biophysical Society of Japan in November 2023 follows the one organized in 2022 [4]. The 2023 symposium aims to learn about the trans-scale interactions between organisms and the environment (Figure 1). It starts with two speakers who study heat release within a biomolecule. The third speaker considers thermal responses of biomolecules and cells. They focus mainly on the spatial scales of atoms, molecules and cells. Their interdisciplinary approaches include biophysics, computational chemistry, and material science. The fourth speaker then presents fluorescent probes for quantitative imaging of intracellular kinase activity. The final speaker demonstrates the use of advanced robotics to study the interactions at the organismal level.
The first presentation is by Ikuo Kurisaki. He and his colleagues have previously examined the conversion of chemical energy derived from GTP hydrolysis into mechanical work by a small GTPase protein, Ras, in the framework of classical molecular dynamics simulation [2,5]. In the current symposium, his talk entitled “Mechanical work generation at early stage of ATP hydrolysis in myosin” focuses on the early stage of ATP hydrolysis to investigate how an ATPase, myosin, converts the chemical energy of ATP into mechanical work. He uses the force field switching technique to microscopically examine the relaxation process of the potential and kinetic energies of the catalytic domain of myosin during the chemical conversion of ATP into ADP and Pi. The calculation demonstrates an increase in the potential energy of the P-loop in myosin.
The second presentation, entitled “Spaciotemporal mapping of vibrational energy flow in proteins” by Misao Mizuno, presents an advanced method for mapping the vibrational energy flow in a protein with the spatial resolution of a single amino acid residue using time-resolved anti-Stokes resonance Raman spectroscopy [6]. The Raman bands of amino acid residues provide information on the local temperature in proteins under non-equilibrium conditions. For example, spectroscopic thermometry estimated the increase in local temperature at the tryptophan residue in cytochrome c after photoexcitation to be approximately 130–150 K [7]. Molecular thermometry in combination with atomistic simulation has the potential to reveal how biomolecules generate heat and convert it into their mechanical functions in response to environmental stimuli.
Satoshi Arai, a pioneer in chemically designed small molecules for organelle-specific thermometry, presents “Nanothermometry and local heating of lipid membranes using synthetic dyes.” The temperature-sensitive fluorescent dyes that he and his colleagues have developed selectively localize to either mitochondria, endoplasmic reticulum, plasma membrane, lysosomes, Golgi, nuclei, or lipid droplets [8]. Fluorescence lifetime-based thermometry revealed an intracellular temperature gradient during cellular thermogenesis. They also developed a polymeric nanoparticle, nanoheater-thermometer (nanoHT), for local heating and temperature sensing [9]. The nanoHT induced rapid death of cancer cells and contraction of C2C12 myotubes. Accurate manipulation of local temperature has the potential to develop effective thermal therapy for cancer and muscle.
Intracellular signaling can be rapidly perturbed by external stimuli. As a specific example of such signaling, quantitative fluorescence imaging of kinase activity is introduced in the fourth talk of the symposium. Taichiro Tomida, a specialist in stress-activated signaling at the single cell level [10–12], presents “Dynamics and function of stress-activated MAPK signaling in determining cell fates.” The mitogen-activated protein kinase (MAPK) family is activated by environmental stresses, including ultraviolet, oxidative stress, and hyperosmotic stress. To monitor MAPK activity, Taichiro has developed a Förster resonance energy transfer (FRET)-based sensor that changes its signal when phosphorylated by MAPK. His systematic analysis by applying various patterns of input (stress) and quantitative imaging of output (MAPK activity and downstream signaling) has revealed the mechanism of stress-activated signal transduction.
In the last presentation, entitled “An engineering approach to investigate the various adaptive behavior derived from the interaction between the body and the environment,” Yasuhiro Sugimoto discusses how state-of-the-art robots can be used as a constructive approach to successfully examine organism-environment interactions. He and his colleagues have investigated adaptive behaviors derived from the interaction between the body and the environment, using various walking behaviors of insects and insect fighting behaviors as models [13–14]. Elucidating the mechanisms of adaptive behaviors will be beneficial to both biology and robotics design. This presentation inspires novel applications of robotics in biophysics.
In summary, this symposium focuses on interdisciplinary approaches to study the interaction of biological systems with the environment at all spatial scales of biological systems. Single approaches have a limited range of scales that they can cover. We expect that hybrid biophysics, which combines multiple interdisciplinary approaches, will be actively employed in the trans-scale analysis of organelle-environment interactions.
The authors thank all the invited speakers of this symposium. This work and symposium are partly supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) “Grant-in-Aid for Transformative Research Areas (B),” “Trans-scale thermal signaling in muscle” (JP22H05052).
