A primary cilium, made of nine microtubule doublets enclosed in a cilium membrane, is a mechanosensing organelle that bends under an external mechanical load and sends an intracellular signal through transmembrane proteins activated by cilium bending. The nine microtubule doublets are the main load-bearing structural component, while the transmembrane proteins on the cilium membrane are the main sensing component. No distinction was made between these two components in all existing models, where the stress calculated from the structural component (nine microtubule doublets) was used to explain the sensing location, which may be totally misleading. For the first time, we developed a microstructure-based primary cilium model by considering these two components separately. First, we refined the analytical solution of bending an orthotropic cylindrical shell for individual microtubule, and obtained excellent agreement between finite element simulations and the theoretical predictions of a microtubule bending as a validation of the structural component in the model. Second, by integrating the cilium membrane with nine microtubule doublets and simulating the tip-anchored optical tweezer experiment on our computational model, we found that the microtubule doublets may twist significantly as the whole cilium bends. Third, besides being cilium-length-dependent, we found the mechanical properties of the cilium are also highly deformation-dependent. More important, we found that the cilium membrane near the base is not under pure in-plane tension or compression as previously thought, but has significant local bending stress. This challenges the traditional model of cilium mechanosensing, indicating that transmembrane proteins may be activated more by membrane curvature than membrane stretching. Finally, we incorporated imaging data of primary cilia into our microstructure-based cilium model, and found that comparing to the ideal model with uniform microtubule length, the imaging-informed model shows the nine microtubule doublets interact more evenly with the cilium membrane, and their contact locations can cause even higher bending curvature in the cilium membrane than near the base.
We have developed a numerical model of two osculating cylindrical elastic renal tubules to investigate the impact of neighboring tubules on the stress applied to a primary cilium. We hypothesize that the stress at the base of the primary cilium will depend on the mechanical coupling of the tubules due to local constrained motion of the tubule wall. The objective of this work was to determine the in-plane stresses of a primary cilium attached to the inner wall of one renal tubule subject to the applied pulsatile flow, with a neighboring renal tube filled with stagnant fluid in close proximity to the primary tubule. We used the commercial software COMSOLⓇ to model the fluid-structure interaction of the applied flow and tubule wall, and we applied a boundary load to the face of the primary cilium during this simulation to produces a stress at its base. We confirm our hypothesis by observing that on average the in-plane stresses are greater at the base of the cilium when there is a neighboring renal tube versus if there is no neighboring tube at all. In combination with the hypothesized function of a cilium as a biological fluid flow sensor, these results indicate that flow signaling may also depend on how the tubule wall is constrained by neighboring tubules. Our results may be limited in their interpretation due to the simplified nature of our model geometry, and further improvements to the model may potentially lead to the design of future experiments.
"Gravity, magnetic and electromagnetic gradiometry: strategic technologies in the 21st century, 2nd edition." Contemporary Physics, ahead-of-print(ahead-of-print), p. 1
Fluorescence correlation spectroscopy (FCS) was developed because dynamic light scattering (DLS) became an essential laboratory technique.Dynamic light scatteringmonitors fluctuations in light scattered by a macroscopic sample to infer microscopic dynamical properties (viscosity, diffusion constants, etc.), and the application of DLS to a fluorescence microscope resulted in FCS. This is not to say that FCS is trivial to implement! The essential procedure in FCS analysis is to fit the measured correlation functions to a model that describes the process (e.g. diffusion). Obtaining the correlation function can be done either with hardware (correlation cards) or software routines; the data itself could come frommeasuring the intensity within a small focal volume of a confocal microscope over time. Data acquisition could also be measuring the fluctuating intensity of two nearby focal volumes and computing the cross-correlation. This text is suitable either for students and researchers who are unfamiliar with FCS as well as those who have some limited exposure to the technique and wish to deepen their understanding. The first four chapters are devoted to background information: parts of a fluorescencemicroscope (including confocal), the mathematics of correlation functions, and basic data processing routines. These chapters are written in an informal, conversational style. Chapter 5 is concerned with obtainingmodel correlation functions for a variety of diffusion processes: free diffusion in 2-D or 3-D, anomalous diffusion, diffusion in the presence of flow (active transport), etc. A table at the end of this chapter lists 14 different model solutions. Similarly, Chapter 6 is concerned with obtaining model solutions for crosscorrelation spectroscopy, when there are multiple distinct intensity signals. Note, this can be applied to the use of two differently-labeled species within the same focal volume, so called dual-color FCS. The models are more complex as different focal volumes could have different sizes or shapes and partially overlap with each other. And more, there could be (fluorescent) spectral crosstalk, quenching processes, FRET and other effects that alter the correlation signal and need to be accounted for in model solutions. It is a particular strength of this text that the authors carefully and explicitly walk the reader through all of this. Appropriately, after two intenselymathematical chapters, the authors pivot to two chapters concerned with data artifacts (Chapter 7) and data fitting (Chapter 8). Personally, I appreciated the care and candor the authors use when discussing artifacts – the underlying physical mechanisms, for example the effect of photobleaching on the autocorrelation function – and detailed discussions about how these artifacts can be addressed and mitigated. Similarly, I have a new appreciation for the subtle aspects of FCS data fitting: specifically, choosing ∗which∗ model ACF function should be chosen to fit ∗to∗. The penultimate chapter ties everything together, providing measurement strategies when designing experiments. Throughout the book, there are end-of-chapter exercises with solutions provided in an Appendix. Unfortunately, there is no index which does make finding specific information more time-consuming. In conclusion, this text is an excellent introduction to the theory and practice of Fluorescence Correlation Spectroscopy, possibly the best place to start for those interested in adding this technique to their laboratory.
Absinthe is an anise-flavored alcohol that is typically served by adding cold water to form a cloudy green louche, similar to the cloudy white louche of ouzo. This microemulsion formation, due to the competing interactions within the oil-alcohol-water system, has been termed the ouzo effect. Previous work has examined the ternary oil-alcohol-water phase diagram in ouzo and limoncello. Additional work has also characterized the droplet size and stability of microemulsions in ouzo, limoncello, and pastis. However, less work has been done to examine the effect of temperature on louche formation despite the fact that the louche is traditionally formed by adding ice cold water. This work demonstrates that both the maximum turbidity and the fraction of alcohol at maximum turbidity are temperature-dependent. The louche formation can be fit with a logistic curve, and the resulting fit parameters are linear with temperature. Optical images show that the increased turbidity correlates with an increase in the number of droplets in the microemulsion.
Primary cilia are non-motile, solitary (one per cell) microtubule-based organelles that emerge from the mother centriole after cells have exited the mitotic cycle. Identified as a mechanosensing organelle that responds to both mechanical and chemical stimuli, the primary cilium provides a fertile ground for integrative investigations of mathematical modeling, numerical simulations, and experiments. Recent experimental findings revealed considerable complexity to the underlying mechanosensory mechanisms that transmit extracellular stimuli to intracellular signaling many of which include primary cilia. In this invited review, we provide a brief survey of experimental findings on primary cilia and how these results lead to various mathematical models of the mechanics of the primary cilium bent under an external forcing such as a fluid flow or a trap. Mathematical modeling of the primary cilium as a fluid-structure interaction problem highlights the importance of basal anchorage and the anisotropic moduli of the microtubules. As theoretical modeling and numerical simulations progress, along with improved state-of-the-art experiments on primary cilia, we hope that details of ciliary regulated mechano-chemical signaling dynamics in cellular physiology will be understood in the near future.
We develop a physics-based kinematic model of martial arts movements incorporating rotation and angular momentum, extending prior analyses. Here, our approach is designed for a classroom environment; we begin with a warm-up exercise introducing counter-intuitive aspects of rotational motion before proceeding to a set of model collision problems that are applied to martial arts movements. Finally, we develop a deformable solid-body mechanics model of a martial arts practitioner suitable for an intermediate mechanics course. We provide evidence for our improved model based on calculations from biomechanical data obtained from prior reports as well as time-lapse images of several different kicks. In addition to incorporating angular motion, our model explicitly makes reference to friction between foot and ground as an action-reaction pair, showing that this interaction provides the motive force/torque for nearly all martial arts movements. Moment-of-inertia tensors are developed to describe kicking movements and show that kicks aimed high, towards the head, transfer more momentum to the target than kicks aimed lower, e.g. towards the body.
‘Waves and Rays in Seismology’ is a fascinating text devoted to the application of continuum mechanics to seismology. A crucial fact is laid out in the first sentence in the Forward: ‘Seismology, s...
‘X-ray Microscopy’, in the main, covers X-ray optical systems with special emphasis on microscopy. As someone with many years of UV-Vis-IR optical experience, I did not truly understand the ‘great ...
The overall theme of this book is obtaining and analysing solutions to discretised parameter estimation problems using both classical and Bayesian approaches. Briefly, ‘parameter estimation’ is the...
Operation STEM (OpSTEM) is a NSF grant-funded program in the USA to improve retention and graduation among high-risk students seeking STEM degrees by supporting them through early mathematics. OpSTEM focuses on students from underrepresented minority (URM) groups, first-generation college students, and women. The OpSTEM program has two levels of treatment: supplemental instruction and a comprehensive program. This study considers URM students and their non-URM counterparts. For non-URM students, the majority of gains are seen in pass rates with supplemental instruction. The comprehensive program is associated with increases in pass rates such that URM students are indistinguishable from their non-URM counterparts. For URM students, a comprehensive program is associated with a narrowing of the achievement gap that is not found with supplemental instruction alone.
‘X-ray Microscopy’, in the main, covers X-ray optical systems with special emphasis on microscopy. As someone with many years of UV-Vis-IR optical experience, I did not truly understand the ‘great ...
I absolutely love discovering books like this, one that rewards the curious reader. It’s a highly engaging account of a specialised, somewhat obscure, technical field that has a clear application t...
According to the contents of Professor Ladd’s engaging book, the essence of Crystallography is group theory, and specifically space groups. Much of his book consists of the theory and application o...
This is an unusual textbook, for two reasons. First, any attempt to cover both quantum physics and special relativity in a self-contained manner within a book less than 300 pages long is audacious. Second, one of the authors’ main goals of this text is to ‘convey how quantumphysics and relativity form an important part of our cultural and intellectual heritage’ – in the context of a physics textbook, this is a peculiar choice of words. I definitely agree with the authors, this textbook is unique. Let me first begin by clearly stating that the authors have done an exceptional job. It’s probably more accurate to describe this text as an introduction to both non-relativistic and relativistic quantum mechanics (QM). Indeed, the first half of the book is devoted to non-relativistic QM, followed by a single chapter on Special Relativity. The second half of the book content primarily consists of relativistic corrections to QM (fine structure, etc.) and a final chapter on ‘Entanglement’. The scope of this textbook is dizzying, to say the least. For example, two-level systems are covered in barely more than a single page, and a free particle given half that amount of space. Quantum field theory is disposed of in 4 pages. This is the price paid to keep the textbook length below 300 pages. It’s not entirely clear who the audience for this textbook is. Clearly, this book could form the basis for a ‘Physics III’ or ‘Modern Physics’ course, but it could also serve as the sourcebook for an introductory QM course. I would be very cautious about using this book as a self-study text for reasons that I will explain shortly. Personally, I would be likely to use this textbook as a supplement. The authors’ idiosyncratic approach provides brief discussions of several topics I would like to touch on in my own QM courses: cold matter and entanglement purification, for example. I also greatly appreciate the occasional use of thermodynamic arguments to obtain results—an approach rarely encountered in other QM texts. Having (too) brief sectionsmeans that I can easily find ‘refresher’ discussions about nearly every topic I cover in a 2-semester QM course. Lastly, the example problems provided at the end of each chapter (and answers provided at the end of the book, in Chapter 13) span a useful range of difficulty. Now for my concern. I want to be clear: in my experience, QM textbooks reflect a far wider range of idiosyncratic approaches than any other branch of science. This is not inherently bad. My concern is the varying level of mathematical sophistication employed. Certainly, the first four chapters are at a level typically associated with introductoryQM: basic calculus and a single differential equation (Schroedinger’s). However, in Chapter 8 (‘Formal structure of QM’), Dirac notation suddenly appears along with the attendant body of linear algebra. Operators are introduced as needed, without any real systematic discussion: raising and lowering operators appear in Chapter 4, well before any notion of linear algebra has been discussed. If there is a knowledgable instructor who can help guide the students, this is less of a concern. However, it does limit the self-study capability of this book. Regardless, this book was a lot of fun to read and digest. I definitely recommend it for instructors, but also for students who have already been exposed toQM.Kudos to the authors for pulling off such an audacious feat.
The fluctuating position of an optically trapped cilium tip under untreated and Taxol-treated conditions was used to characterize mechanical properties of the cilium axoneme and its basal body by combining experimental, analytical, and computational tools. We provide, for the first time, evidence that the persistence length of a ciliary axoneme is length-dependent; longer cilia are stiffer than shorter cilia. We demonstrate that this apparent length dependence can be understood by a combination of modeling axonemal microtubules as anisotropic elastic shells and including actomyosin-driven stochastic basal body motion. Our results also demonstrate the possibility of using observable ciliary dynamics to probe interior cytoskeletal dynamics. It is hoped that our improved characterization of cilia will result in deeper understanding of the biological function of cellular flow sensing by this organelle.