Calculating New Parameters.

Abstract

Mathematics is biology's next microscope, only better; biology is mathematics’ next physics, only better. – Joel CohenHistorically, studies in biology were performed by those in the physical sciences: physicists, mathematicians, chemists, and engineers. Many subdisciplines of biology owe their existence to the physical sciences: the ‘father of modern genetics’, Gregor Mendel, revealed the basic laws of heredity through mathematics, while the structure of DNA–and the dawn of molecular biology – was approached as a physics problem. Even the birth of cell biology relied on viewing aggregates of cells under a light microscope – a tool that demanded knowledge in optical engineering. So, if the physical sciences have given biologists so much, why have many largely abandoned their principles?It is true, cell biologists are more comfortable with biochemical and genetic approaches, rather than physical ones, and molecular tools have provided us with an exhaustive list of biomolecules and molecular pathways, ranging from the cellular to the organismal level. However, the challenge remains: how do these parts work together to guide cell processes? This level of clarity demands the quantitative problem-solving skills of the physical sciences. Efforts to bridge the gap between the biological and physical sciences are beginning. A quick glance through an abstract book from a recent cell biology meeting will reveal an astonishing number of topics using quantitative analysis. Trends in Cell Biology recognizes this pivotal shift in the foundations of cell biology, and this special issue explores the importance of physical and quantitative approaches in understanding the dynamics of cellular systems.The physical sciences have made the largest impact on cell biology through the development of tools. In particular, advances in microscopy have enabled the characterization, movement, and dynamics of proteins in living cells. Covering this area, Vito Mennella and colleagues review how super-resolution microscopy is providing insight into the nanoscopic organization of proteins that give rise to cellular structures. Some techniques were designed for quantitative analysis, whereas others are ripe for the taking. William Greenleaf and Viviana Risca describe recent approaches to utilize sequencing tools, such as paired-end sequencing to quantitatively understand genome structure. Gaudenz Danuser and Meghan Driscoll detail the measures that need to be taken to quantify cell migration in three dimensions, which will allow investigators to probe cellular functions in more realistic microenvironments.Since cell biologists are likely not well-versed in theoretical physics or mathematical modeling, interdisciplinary approaches between researchers from both the biological and physical sciences will be crucial. Ewa Paluch discusses how these disciplines can foster collaboration for scientific advancement. A major difference between the fields is how each defines a model. For cell biologists, a model often manifests itself as a cartoon summarizing available data at the end of an article, while physical scientists introduce a model first, so that it can be tested against physical principles. Rob Phillips reveals the power of models and urges cell biologists to reconsider its role when addressing their next problem. Whole-cell modeling, in particular, can allow assumptions to be made and tested based on combined observations at different scales, and Markus Covert and Javier Carrera argue how this approach will facilitate biological discovery.The remaining articles explore the power of quantitative studies on some of the most basic, but important questions in cell biology: How do cells grow? How do cells determine their shape? How do molecules know when and where to move inside cells? Wallace Marshall examines the ways in which cells sense and measure length on subcellular scales to solve cell geometry problems. Articles from Joe Howard and colleagues and from Patricia Bassereau and colleagues extend these concepts to the mechanics of the cytoskeleton and membrane function, respectively. On the cellular scale, Jan Skotheim and colleagues describe recently identified molecular mechanisms by which cells coordinate growth and division. Moving up in scale, two articles reveal the application of physical principles in cell communication within an environment. Brenton Hoffman and Alpha Yap rationalize how mechanically sensitive cadherin junctions can operate across different time scales, and Daniel Riveline and colleagues describe a new mode of migration, known as ratchetaxis that was identified through quantitative experiments and mathematical modeling. While these reviews make clear that theories from the physical sciences can provide a basis to explain self-organization and dynamics of cellular processes, Daniel Needleman also reminds readers that current physical models can only take us so far and that comparisons between theory and experiment may require us to revise models of more complex cellular organizations.I hope that these reviews reveal the power of quantitative approaches for the study of cell biological problems, and inspire cell biologists to embrace the principles that physical sciences have brought forth. To address some of the most complex questions in biology, it will not be enough to only apply the tools provided by the physical sciences, but rather the fundamental approaches of the physical sciences – quantitative and multivariate – will need to be integrated into the core of cell biology. Quantitative analysis will allow observations to be tested in a more formalized and structured manner, bringing cell biologists one step closer to understanding how the parts make the whole.I thank all the authors and reviewers for their contributions to the special issue, and I thank you for reading it. I would also like to send a sincere thank you to the faculty of the Marine Biological Laboratory Physiology Course, who made me a believer in the powers of the physical sciences. Your comments and ideas are always welcome; you can contact us with feedback or questions at [email protected] or @TrendsCellBio. Mathematics is biology's next microscope, only better; biology is mathematics’ next physics, only better. – Joel Cohen Historically, studies in biology were performed by those in the physical sciences: physicists, mathematicians, chemists, and engineers. Many subdisciplines of biology owe their existence to the physical sciences: the ‘father of modern genetics’, Gregor Mendel, revealed the basic laws of heredity through mathematics, while the structure of DNA–and the dawn of molecular biology – was approached as a physics problem. Even the birth of cell biology relied on viewing aggregates of cells under a light microscope – a tool that demanded knowledge in optical engineering. So, if the physical sciences have given biologists so much, why have many largely abandoned their principles? It is true, cell biologists are more comfortable with biochemical and genetic approaches, rather than physical ones, and molecular tools have provided us with an exhaustive list of biomolecules and molecular pathways, ranging from the cellular to the organismal level. However, the challenge remains: how do these parts work together to guide cell processes? This level of clarity demands the quantitative problem-solving skills of the physical sciences. Efforts to bridge the gap between the biological and physical sciences are beginning. A quick glance through an abstract book from a recent cell biology meeting will reveal an astonishing number of topics using quantitative analysis. Trends in Cell Biology recognizes this pivotal shift in the foundations of cell biology, and this special issue explores the importance of physical and quantitative approaches in understanding the dynamics of cellular systems. The physical sciences have made the largest impact on cell biology through the development of tools. In particular, advances in microscopy have enabled the characterization, movement, and dynamics of proteins in living cells. Covering this area, Vito Mennella and colleagues review how super-resolution microscopy is providing insight into the nanoscopic organization of proteins that give rise to cellular structures. Some techniques were designed for quantitative analysis, whereas others are ripe for the taking. William Greenleaf and Viviana Risca describe recent approaches to utilize sequencing tools, such as paired-end sequencing to quantitatively understand genome structure. Gaudenz Danuser and Meghan Driscoll detail the measures that need to be taken to quantify cell migration in three dimensions, which will allow investigators to probe cellular functions in more realistic microenvironments. Since cell biologists are likely not well-versed in theoretical physics or mathematical modeling, interdisciplinary approaches between researchers from both the biological and physical sciences will be crucial. Ewa Paluch discusses how these disciplines can foster collaboration for scientific advancement. A major difference between the fields is how each defines a model. For cell biologists, a model often manifests itself as a cartoon summarizing available data at the end of an article, while physical scientists introduce a model first, so that it can be tested against physical principles. Rob Phillips reveals the power of models and urges cell biologists to reconsider its role when addressing their next problem. Whole-cell modeling, in particular, can allow assumptions to be made and tested based on combined observations at different scales, and Markus Covert and Javier Carrera argue how this approach will facilitate biological discovery. The remaining articles explore the power of quantitative studies on some of the most basic, but important questions in cell biology: How do cells grow? How do cells determine their shape? How do molecules know when and where to move inside cells? Wallace Marshall examines the ways in which cells sense and measure length on subcellular scales to solve cell geometry problems. Articles from Joe Howard and colleagues and from Patricia Bassereau and colleagues extend these concepts to the mechanics of the cytoskeleton and membrane function, respectively. On the cellular scale, Jan Skotheim and colleagues describe recently identified molecular mechanisms by which cells coordinate growth and division. Moving up in scale, two articles reveal the application of physical principles in cell communication within an environment. Brenton Hoffman and Alpha Yap rationalize how mechanically sensitive cadherin junctions can operate across different time scales, and Daniel Riveline and colleagues describe a new mode of migration, known as ratchetaxis that was identified through quantitative experiments and mathematical modeling. While these reviews make clear that theories from the physical sciences can provide a basis to explain self-organization and dynamics of cellular processes, Daniel Needleman also reminds readers that current physical models can only take us so far and that comparisons between theory and experiment may require us to revise models of more complex cellular organizations. I hope that these reviews reveal the power of quantitative approaches for the study of cell biological problems, and inspire cell biologists to embrace the principles that physical sciences have brought forth. To address some of the most complex questions in biology, it will not be enough to only apply the tools provided by the physical sciences, but rather the fundamental approaches of the physical sciences – quantitative and multivariate – will need to be integrated into the core of cell biology. Quantitative analysis will allow observations to be tested in a more formalized and structured manner, bringing cell biologists one step closer to understanding how the parts make the whole. I thank all the authors and reviewers for their contributions to the special issue, and I thank you for reading it. I would also like to send a sincere thank you to the faculty of the Marine Biological Laboratory Physiology Course, who made me a believer in the powers of the physical sciences. Your comments and ideas are always welcome; you can contact us with feedback or questions at [email protected] or @TrendsCellBio.