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Journal of Neuroscience Methods Oct 2020The biophysical modeling efforts in diffusion MRI have grown considerably over the past 25 years. In this review, we dwell on the various challenges along the journey of... (Review)
Review
The biophysical modeling efforts in diffusion MRI have grown considerably over the past 25 years. In this review, we dwell on the various challenges along the journey of bringing a biophysical model from initial design to clinical implementation, identifying both hurdles that have been already overcome and outstanding issues. First, we describe the critical initial task of selecting which features of tissue microstructure can be estimated using a model and which acquisition protocol needs to be implemented to make the estimation possible. The model performance should necessarily be tested in realistic numerical simulations and in experimental data - adapting the fitting strategy accordingly, and parameter estimates should be validated against complementary techniques, when/if available. Secondly, the model performance and validity should be explored in pathological conditions, and, if appropriate, dedicated models for pathology should be developed. We build on examples from tumors, ischemia and demyelinating diseases. We then discuss the challenges associated with clinical translation and added value. Finally, we single out four major unresolved challenges that are related to: the availability of a microstructural ground truth, the validation of model parameters which cannot be accessed with complementary techniques, the development of a generalized standard model for any brain region and pathology, and the seamless communication between different parties involved in the development and application of biophysical models of diffusion.
Topics: Biophysics; Brain; Diffusion; Diffusion Magnetic Resonance Imaging
PubMed: 32692999
DOI: 10.1016/j.jneumeth.2020.108861 -
ELife Mar 2019Computational models are helping researchers to understand how certain properties of neurons contribute to respiratory rhythms.
Computational models are helping researchers to understand how certain properties of neurons contribute to respiratory rhythms.
Topics: Animals; Biophysics; Models, Neurological; Neurons; Respiration
PubMed: 30907725
DOI: 10.7554/eLife.46033 -
Nature Materials Nov 2017Biomaterials engineered with specific bioactive ligands, tunable mechanical properties, and complex architectural features have emerged as powerful tools to probe how... (Review)
Review
Biomaterials engineered with specific bioactive ligands, tunable mechanical properties, and complex architectural features have emerged as powerful tools to probe how cells sense and respond to the physical properties of their material surroundings, and ultimately provide designer approaches to control cell function.
Topics: Animals; Biocompatible Materials; Biomechanical Phenomena; Biophysics; Humans
PubMed: 29170549
DOI: 10.1038/nmat5049 -
Cells Apr 2021Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological... (Review)
Review
Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological processes is particularly important for immune cells in the context of the dynamic and complex tissue microenvironment. However, it remains largely unknown how cellular mechanical force generation and mechanical properties are regulated and integrated by immune cells, primarily due to a profound lack of technologies with sufficient sensitivity to quantify immune cell mechanics. In this review, we discuss the biological significance of mechanics for immune cells across length and time scales, and highlight several experimental methodologies for quantifying the mechanics of immune cells. Finally, we discuss the importance of quantifying the appropriate mechanical readout to accelerate insights into the mechanobiology of the immune response.
Topics: Animals; Biomechanical Phenomena; Biophysics; Humans; Leukocytes; Models, Biological
PubMed: 33918573
DOI: 10.3390/cells10040851 -
Small (Weinheim An Der Bergstrasse,... Feb 2022Embryonic morphogenesis is a biological process which depicts shape forming of tissues and organs during development. Unveiling the roles of mechanical forces generated,... (Review)
Review
Embryonic morphogenesis is a biological process which depicts shape forming of tissues and organs during development. Unveiling the roles of mechanical forces generated, transmitted, and regulated in cells and tissues through these processes is key to understanding the biophysical mechanisms governing morphogenesis. To this end, it is imperative to measure, simulate, and predict the regulation and control of these mechanical forces during morphogenesis. This article aims to provide a comprehensive review of the recent advances on mechanical properties of cells and tissues, generation of mechanical forces in cells and tissues, the transmission processes of these generated forces during cells and tissues, the tools and methods used to measure and predict these mechanical forces in vivo, in vitro, or in silico, and to better understand the corresponding regulation and control of generated forces. Understanding the biomechanics and mechanobiology of morphogenesis will not only shed light on the fundamental physical mechanisms underlying these concerted biological processes during normal development, but also uncover new information that will benefit biomedical research in preventing and treating congenital defects or tissue engineering and regeneration.
Topics: Biomechanical Phenomena; Biophysics; Embryonic Development; Morphogenesis
PubMed: 34837328
DOI: 10.1002/smll.202103466 -
Bone Oct 2021Mechanical environment has a crucial role in our organism at the different levels, ranging from cells to tissues and our own organs. This regulatory role is especially... (Review)
Review
Mechanical environment has a crucial role in our organism at the different levels, ranging from cells to tissues and our own organs. This regulatory role is especially relevant for bones, given their importance as load-transmitting elements that allow the movement of our body as well as the protection of vital organs from load impacts. Therefore bone, as living tissue, is continuously adapting its properties, shape and repairing itself, being the mechanical loads one of the main regulatory stimuli that modulate this adaptive behavior. Here we review some key results of bone mechanobiology from computational models, describing the effect that changes associated to the mechanical environment induce in bone response, implant design and scaffold-driven bone regeneration.
Topics: Biophysics; Bone Regeneration; Bone and Bones; Prostheses and Implants
PubMed: 34118446
DOI: 10.1016/j.bone.2021.116032 -
The Journal of General Physiology Dec 2018Sobolevsky reflects on his unique scientific upbringing in Russia.
Sobolevsky reflects on his unique scientific upbringing in Russia.
Topics: Biophysics; History, 20th Century; History, 21st Century; Russia; Universities
PubMed: 30459255
DOI: 10.1085/jgp.201812265 -
International Journal of Molecular... Jun 2023Though microscopy is most often intended as a technique for providing qualitative assessment of cellular and subcellular properties, when coupled with other instruments... (Review)
Review
Though microscopy is most often intended as a technique for providing qualitative assessment of cellular and subcellular properties, when coupled with other instruments such as wavelength selectors, lasers, photoelectric devices and computers, it can perform a wide variety of quantitative measurements, which are demanding in establishing relationships between the properties and structures of biological material in all their spatial and temporal complexities. These combinations of instruments are a powerful approach to improve non-destructive investigations of cellular and subcellular properties (both physical and chemical) at a macromolecular scale resolution. Since many subcellular compartments in living cells are characterized by structurally organized molecules, this review deals with three advanced microscopy techniques well-suited for these kind of investigations, i.e., microspectrophotometry (MSP), super-resolution localization microscopy (SRLM) and holotomographic microscopy (HTM). These techniques can achieve an insight view into the role intracellular molecular organizations such as photoreceptive and photosynthetic structures and lipid bodies play in many cellular processes as well as their biophysical properties. Microspectrophotometry uses a set-up based on the combination of a wide-field microscope and a polychromator, which allows the measurement of spectroscopic features such as absorption spectra. Super resolution localization microscopy combines dedicated optics and sophisticated software algorithms to overcome the diffraction limit of light and allow the visualization of subcellular structures and dynamics in greater detail with respect to conventional optical microscopy. Holotomographic microscopy combines holography and tomography techniques into a single microscopy set-up, and allows 3D reconstruction by means of the phase separation of biomolecule condensates. This review is organized in sections, which for each technique describe some general aspects, a peculiar theoretical aspect, a specific experimental configuration and examples of applications (fish and algae photoreceptors, single labeled proteins and endocellular aggregates of lipids).
Topics: Animals; Microscopy, Fluorescence; Proteins; Optics and Photonics; Biophysics; Holography
PubMed: 37373120
DOI: 10.3390/ijms24129973 -
International Journal of Molecular... Oct 2021Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years,... (Review)
Review
Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years, calcineurin has been the subject of extensive investigation. Many of its cellular and physiological functions have been described, and the underlying biophysical mechanisms are the subject of active investigation. With the abundance of techniques and experimental designs utilized to study calcineurin and its numerous substrates, it is difficult to reconcile the available information. There have been a plethora of reports describing the role of calcineurin in cardiac disease. However, a physiological role of calcineurin in healthy cardiomyocyte function requires clarification. Here, we review the seminal biophysical and structural details that are responsible for the molecular function and inhibition of calcineurin. We then focus on literature describing the roles of calcineurin in cardiomyocyte physiology and disease.
Topics: Animals; Biophysics; Calcineurin; Heart; Heart Diseases; Humans; Myocytes, Cardiac; Signal Transduction
PubMed: 34768996
DOI: 10.3390/ijms222111565 -
Communications Biology Jun 2021Endothelial cells (ECs) lining all blood vessels are subjected to large mechanical stresses that regulate their structure and function in health and disease. Here, we... (Review)
Review
Endothelial cells (ECs) lining all blood vessels are subjected to large mechanical stresses that regulate their structure and function in health and disease. Here, we review EC responses to substrate-derived biophysical cues, namely topography, curvature, and stiffness, as well as to flow-derived stresses, notably shear stress, pressure, and tensile stresses. Because these mechanical cues in vivo are coupled and are exerted simultaneously on ECs, we also review the effects of multiple cues and describe burgeoning in vitro approaches for elucidating how ECs integrate and interpret various mechanical stimuli. We conclude by highlighting key open questions and upcoming challenges in the field of EC mechanobiology.
Topics: Anisotropy; Biophysics; Blood Pressure; Cell Count; Endothelial Cells; Humans; Stress, Mechanical
PubMed: 34155305
DOI: 10.1038/s42003-021-02285-w