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Physics of Life (2022) / Chapter Skim
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Pages 192-213

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From page 192...
... While ecology was the traditional source of nonlinear dynamics problems, genetic networks have formed a productive modern nexus, connecting the biological phys ics community to nonlinear dynamics, but also to the systems and synthetic biology communities (Chapters 6 and 7)
From page 193...
... This is a very active field, with theory now being supplemented by large scale, controlled experiments in microbial ecologies. Finally, what about the connection of biological physics to the physics of the universe as a whole?
From page 194...
... Regarding the deep history of life on Earth, there are classical experiments showing that early atmospheric conditions allowed for the synthesis of moderately complex organic molecules, including amino acids. But there is a huge gap from this to something one might think of as alive.
From page 195...
... R e l at i o n to Other Fields of Physics 195 molecules of life on Earth form a network with special properties, distinguished from a random jumble of molecules of similar size and elemental composition. Perhaps the most important result of thinking more concretely about how to search for life on extra-solar planets is that we are not so sure what features of life on Earth constitute its defining physical characteristics.
From page 196...
... Part I of this report is focused on how the phenomena of life generate questions for the physics community. In that process, knowledge gathered in the biology community provides a foundation for asking new physics questions about the phenomena of life, and ultimately for discovery of new physics.
From page 197...
... Fluorescence Microscopy Becomes Dominant Fluorescence microscopy techniques have had especially great influence on biological physics investigations, and on biology more broadly, particularly in recent decades. This impact is due in large part to the ability to mark and thereby identify specific, chosen components of biological cells with a wide range of different fluorescent dyes, genetically encoded fluorescent proteins, fluorescent nanoparticles, fluorescently labeled nucleic acids, or fluorescent markers of other kinds.
From page 198...
... One important advance from physics that revo lutionized the ability of biologists to visualize the behavior of single fluorescently labeled molecules in a very thin optical section was total internal reflection fluorescence microscopy (TIRFM)
From page 199...
... This has allowed the characterization of the stepping of single motor proteins along cytoskeletal filaments or DNA, statistics of single protein-protein binding interactions, and microrheological measurements of material properties, to name a few. By achieving a more versatile form of optical sectioning and enabling threedimensional imaging at the sub-micron scale, confocal fluorescence microscopy revealed many new facets of cells and tissues.
From page 200...
... between a pair of single fluorophores, as the efficiency of energy transfer depends on the distance be tween the two molecules and hence provides a "molecular ruler" with the sensitivity to detect changes in macromolecular conformations of less than 10 nanometers. From this field of single molecule biophysics emerged the stochastic localiza tion microscopy techniques as an alternative to STED microscopy for acquiring nanoscopic information.
From page 201...
... Such capabilities have had broad-ranging impact on biological physics and related fields, particularly when microfluidic devices are combined with additional approaches to characterize or manipulate specimens, such as via optical measurements or biochemical reactions. Example applications involving microfluidic control include flow microcytometry analyses of the properties of individual cells, screening of small model organisms (e.g., nematodes, fly embryos, zebrafish larvae)
From page 202...
... Similar new technology is needed in other areas, such as protein and organelle purification, cell and animal care, and the development of transgenic organisms. These frontiers of measurement often are explored by the biological physics community in response to physicist's ques tions about the phenomena of life, but the resulting methods are transferred to the larger biology community at ever increasing rates.
From page 203...
... The overall structure includes 175 subunits with a combined molecular mass of more than 6,000,000 Daltons, and represents a tour de force of structural biology. Shown here is a cross-section through the structure.
From page 204...
... While all these methods have their origins in physics, especially in the biological physics community, there has been a substantial effort to export these methods to a wider range of biologists. This has sped up, enormously, the exploration of the molecular structures relevant to the mechanisms of life.
From page 205...
... Flexibility is essential for function, and few interactions are truly lock and key. The unique analytic powers of NMR have been applied in structural biology and biological physics to clarify these dynamical mechanisms, including identifying allosteric effects in molecular recognition, and especially elucidating the role of conformational exchange in protein function.
From page 206...
... Put another way, what are the physical principles that distinguish functional proteins from all possible polymers of amino acids? As explained in Chapter 3, this prob lem has been a focus of interest in the biological physics community.
From page 207...
... While not so long ago characterization of a single protein was viewed as a major breakthrough, it now is appreciated that each protein is generally linked together with many others into complex "molecular machines" that carry out specialized and coordinated tasks. Approaches from the biological physics community have been helpful, and often necessary, in advancing understanding of the behavior of this molecular machinery and establishing the principles of its function.
From page 208...
... In the biological physics community, this perspective has been pursued in many directions -- to examine the formation of patterns of gene expression in space and time (Chapter 1) , the flow of information through
From page 209...
... Research in biological physics has played a role in developing methods for inference and for analyzing the structure of the resulting genotype–phenotype maps. For example, methods from statistical physics have helped to categorize types of epistasis and analyze how evolution across genotype–phenotype maps with a given statistical structure will tend to lead to regions of the landscape with specific properties.
From page 210...
... CELL AND DEVELOPMENTAL BIOLOGY Cell biology is concerned with elucidating the structure and function of the cell, the "basic unit of life." This field aims to determine how biomolecules self assemble into functioning organelles, or subcellular compartments, that perform specific functions necessary for energy production, waste removal, or self-prop agation; how systems of organelles mediate whole-cell functions such as motility or phagocytosis; and how cells interact with each other and their microenviron ment to mediate tissue-scale physiological functions such as muscle contraction or glandular secretion. The biological physics community has been interested in all these phenomena, and has produced ideas and methods that have spread into the larger cell biology community.
From page 211...
... The biological physics community has contributed to understanding across a range of scales. At the smallest scale, research is aimed at understanding how individual proteins generate and respond to force.
From page 212...
... The notion that cells sense, respond to, and modulate tissue stiffness and vis coelasticity has also had a major impact on cancer cell biology and cancer research more generally. The vast majority of the research effort in cancer has historically been devoted to uncovering the biochemical mechanisms and genomics underly Figure 1.
From page 213...
... Tissue stiffness is an example of an important mechanobiological property. Dysmorphic nuclei are common in cancer, as are changes in chromosome number, and further changes in nuclear properties are emerging.


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