Physics of Life (2022) / Chapter Skim
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Pages 77-103
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From page 77... ...
. The enormous sensitivity of the system has contributions from multiple components: cooperative interactions among neighboring receptor molecules in the cell membrane; a cascade of molecule multiplication not unlike that found in photon counting; and cooperative interactions of the final signaling molecule in controlling the direction of the flagellar motor.
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From page 78... ...
Stereocilia vary systematically in length across each hair bundle and are connected by "tip links" that transmit forces to ion channels in the membrane. In many hair cells, there is a true cilium, the kinocilium, which has a role in organizing and orienting the bundle.
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From page 79... ...
These essentially parameter-free predictions are consistent with classical perceptual observations on "combination tones," and with direct measure ments on hair cells. Perspective This discussion of just three of the very many sensing systems that organisms possess has revealed deep principles.
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From page 80... ...
At the same time, pattern formation in living systems poses qualitatively new challenges, driving the search for new physical principles that can explain these beautiful phenomena. Allometry The first spatial structures of plants and animals that attracted human attention were the most macroscopic, and it would take into the 20th century to state the problem of how these are encoded by the underlying molecules.
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From page 81... ...
Historically, this was important in con vincing the scientific community as a whole that one could, in practice, study the building blocks of life with concepts and methods from physics and chemistry. In modern times, the self-assembly of viruses has emerged as a physics problem, and the interplay between the biological physics community and the larger biology community interested in viruses has led to a field called physical virology, now the subject of regular conferences.
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From page 82... ...
Unfortunately, it is problematic to associ agree well up to the level of amino acid side chain orientations this RNA density with a particular structure (e.g., a dsRN with those determined previously for wild-type BMV -- which hairpin loop)
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From page 83... ...
In many cases, including the well-studied Escherichia coli, the overall structure of the cell is supported in part by a polymer of protein molecules that wraps the cell, underneath its membrane, with a helical structure. This helix has a radius essentially equal to the radius of the cell itself, many hundreds of times larger than the diameter of the constituent protein molecules.
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From page 84... ...
de Boer, 1999, Rapid pole-to-pole oscillation of a protein required for directing division to the middle of Escherichia coli, Proceedings of the National Academy of Sciences U.S.A. 96:4971, Creative Commons License CC BY-NC-ND 4.0.
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From page 85... ...
Within a single cell, what sets the size of organelles? There is a classical example of size regulation in the algal cell Chlamydomonas reinhardtii, which has two flagella of equal length, and this is crucial for its swimming.
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From page 86... ...
In presenting his work, Turing also gave voice to an approach that resonates strongly with many members of the biological physics community even today: A mathematical model of the growing embryo will be described. This model will be a simplification and an idealization, and consequently a falsification.
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From page 87... ...
It will be exciting to see how the examples of self-assembly and pattern formation guide the search for more general physical principles that address this challenge.
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From page 88... ...
Understanding the physics of living systems requires us to understand how information flows across many scales, from single molecules to groups of organisms. From the theoretical side, these explorations often have reinforced the deep connections between statistical physics and information theory, and on the experimental side we have seen the development of extraordinary new measurement techniques.
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From page 89... ...
internal states, all through changing concentrations. The brain 104 Understanding Theories of coding in single New tools for the principles of neurons and large networks; exploring the electrical signal physical limits to information brain; new transmission transmission; connecting ingredients for within cells and molecular dynamics to neural networks across synapses; macroscopic functions.
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From page 90... ...
molecules to amino acids; and in the binding of tRNAs to mRNA during the translation of the mRNA sequence into the amino acid sequence of proteins. In each case living cells achieve a sorting of molecular components that is vastly more accurate than would be expected from energy differences alone.
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From page 91... ...
Similarly, in order to lower the error probabilities in processing information encoded in DNA, the cell expends extra energy in the processes of DNA replication, transcription, tRNA charging, and translation. Although the details vary, all of these processes involve steps that dissipate energy, sometimes in apparently wasteful ways, but these futile steps serve to increase precision.
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From page 92... ...
synthesize, and this mapping from DNA to amino acids is "the genetic code." The genetic code is almost universal across the entire tree of life, although there are important variations. One of the questions that has intrigued both physicists and biologists is whether the code(s)
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From page 93... ...
In bacteria, regulatory sequences often are physically close to the genes that they control. Proteins called transcription factors (TFs)
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From page 94... ...
This is exactly what is expected from the equilibrium statistical mechanics models -- these two numbers are the free energy Model Fit Next we us protein-DN scription. B signs to ea interest, su or the rate multiple p specific m the values dent predi Such m way if we probability quantity of FIGURE 2.2 How much information, in bits, do DNA sequences provide about gene expression?
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From page 95... ...
It now is possible to measure directly the looping of DNA in response to transcription factor binding, although it remains challenging to connect these single molecule experiments to the macroscopic behavior of gene expression, quantitatively. The relatively simple picture of these processes in bacteria, where a small number of transcription factors regulate the expression of nearby genes, stands in contrast to what has been learned about the control of gene expression in higher organisms.
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From page 96... ...
Our immune system also carries a memory, but humans do not pass this information on to their offspring. Theorists in the biological physics community have tried to understand how the different dynamics of environmental challenges drive the emergence of these different strategies in different classes of organisms.
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From page 97... ...
In each of these cases and more, it is reasonable to expect progress in the coming decade both from the introduction of new experimental methods and from the formulation of sharper theoretical questions about how these systems function. INFORMATION IN MOLECULAR CONCENTRATIONS Throughout the living world, information crucial to life's functions is represented or encoded in the concentrations of specific molecules.
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From page 98... ...
On the experimental side, methods from physics have combined with those from chemistry and biology to provide an unprecedented ability to observe and manipulate molecular signals in living cells. These foundational developments set the stage for today's excitement in this crucial area of biological physics.
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From page 99... ...
Many groups in the biological physics community have gone back to the macroscopic features of growth and division in bacteria, discovering for example that fluctuations in growth rate can be inherited and correlations maintained across a dozen generations; the molecules whose concentrations represent this information have not been identified. From Transcription Factors to Genetic Networks An important class of molecules that convey information through their concentrations are transcription factors.
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From page 100... ...
One approach uses microfluidic methods developed in the biological physics community to manipulate large numbers of single cells, ultimately breaking them open and identifying all of their mRNA molecules using biochemical sequencing methods (Chapter 6)
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From page 101... ...
FIGURE 2.5 There is considerable interest from both the biological physics community and the biology community in understanding information flow through networks that control transcription of genes. Toward this end, methods have been developed for counting individual transcripts (i.e., messenger RNA [mRNA]
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From page 102... ...
This positional information is transformed and finally interpreted, in this simple case to make three different cell types that form segments of the body.
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From page 103... ...
In molecular biology, new tools were making it possible to sequence these genes, to synthesize the proteins that they code for in the laboratory, and thus to make probes that could measure their concentration in the embryo. Almost all of the relevant molecules are transcription factors, so these earliest steps in pattern formation involve only the control of gene expression, rather than changes in cell structure or overall geometry of the embryo.
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