Physics of Life (2022) / Chapter Skim
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6 Biology and Chemistry
6 Biology and Chemistry
Pages 196-218
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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.
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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.
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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)
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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.
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From page 200... ...
Notable examples include the discoveries of fine ultrastructure within actin fila ments of the cellular cytoskeleton, recent evidence for phase condensation of RNA polymerase molecules during transcription, unprecedented insights into chromatin structure and its role in gene regulation, and the ability to characterize individual cells based on their RNA expression patterns with near single molecule sensitivity. Microfluidics The field of microfluidics refers to the science and technology of fluidic dy namics at the scales of microliters to femtoliters, at which surface tension and capillary effects have predominant roles.
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From page 201... ...
Microfluidic technology has also helped usher in a new era of so-called single cell "omics," which allow genome-wide studies to be performed at the resolution of individual cells. For instance, biotechnology companies use microfluidics within single cell transcriptomic assays to identify rare populations of diseased cells, such as metastatic cancer cells circulating in the blood; for non-invasive prenatal tests using blood samples from a pregnant mother; and for immune profiling studies, such as to probe a patient's immune system regarding its ability to neutralize viral particles of a new SARS-CoV-2 strain.
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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.
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From page 203... ...
NMR is a particularly useful technique for determining the dynamics of macromolecules in solution as well as membrane proteins in a solid state. Following a dramatic expansion in the early 2010s dubbed the "resolution revolution," cryoEM has now been firmly established alongside MX and NMR as an essential structural biology technique.
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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.
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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.
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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.
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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.
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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
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From page 209... ...
In the first, single cells are routed through microfluidic devices in which their mRNA molecules are extracted, encapsulated in droplets, and then amplified and sequenced (see above)
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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.
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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.
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From page 212... ...
(C) Microarray profiling of MSC cells cultured on 0.1, 1, 11, or 34 with or without blebbistatin treat are normalized to actin levels and ized again to expression in naive ing the fold increase at the bo FIGURE 6.3 The discovery that fate determination could be controlled by the physical cue ofarray.tissue Neurogenic markers (lef highest on 0.1–1 kPa gels, wh stiffness has revolutionized stem cell biology.
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From page 213... ...
The local environment around a tumor -- its microenvironment -- interacts constantly with a tumor and affects its progression. Physical aspects of the tumor microenvironment are known hallmarks of cancers, and there is evidence that they are functionally linked to metabolism, the immune cell interactions with tumors, drug transport into tumors, the proliferation of cells, the ability of cancer cells to develop drug resistance, the ability of cells or clusters of cells to migrate out of the tumor to cause metastasis, and the plasticity of cancer stem cells.
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From page 214... ...
Another recent and major breakthrough in cell biology that came from the bio logical physics community was based on understanding of the principles of phase separation (Chapter 3)
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From page 215... ...
In epithelial cell sheets, the jamming transition is predicted to occur when a single cell shape parameter reaches a specific value; hexagonal cells correspond to solid tissue and deviations from hexagonal are associated with fluidity. An example of a solid-to-fluid transition during development is the onset of neural crest cell migration, which requires a reduction in cell-cell adhesion mediated by internalization of cadherin cell-cell adhesion molecules.
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From page 216... ...
It is well established that embryonic left right patterning is established by fluid flow generated by motile cilia, while midway through embryogenesis, once the heart has formed and started beating, blood flow shapes the development of the vascular network. The development and application of methods to measure and manipulate force, pressure, stiffness, and flow in developing organisms will be key to uncov ering their full role in developmental biology.
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From page 217... ...
Neuroscience as a field was actively constructed from multiple more wellestablished biological disciplines -- physiology and pharmacology, anatomy and cell biology, biochemistry, and more. Perhaps because of this history, there has been a relatively rapid absorption of ideas from the biological physics community into the mainstream of neuroscience.
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From page 218... ...
The physics community's interest in human perception was especially strong, and productive. It is not only that physicists were interested in the mechanics of the ear or the optics of the eye, they also were interested in the inferences that the brain draws from these raw sense data.
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