1,661 research outputs found
Effects of 3D Geometries on Cellular Gradient Sensing and Polarization
During cell migration, cells become polarized, change their shape, and move
in response to various internal and external cues. Cell polarization is defined
through the spatio-temporal organization of molecules such as PI3K or small
GTPases, and is determined by intracellular signaling networks. It results in
directional forces through actin polymerization and myosin contractions. Many
existing mathematical models of cell polarization are formulated in terms of
reaction-diffusion systems of interacting molecules, and are often defined in
one or two spatial dimensions. In this paper, we introduce a 3D
reaction-diffusion model of interacting molecules in a single cell, and find
that cell geometry has an important role affecting the capability of a cell to
polarize, or change polarization when an external signal changes direction. Our
results suggest a geometrical argument why more roundish cells can repolarize
more effectively than cells which are elongated along the direction of the
original stimulus, and thus enable roundish cells to turn faster, as has been
observed in experiments. On the other hand, elongated cells preferentially
polarize along their main axis even when a gradient stimulus appears from
another direction. Furthermore, our 3D model can accurately capture the effect
of binding and unbinding of important regulators of cell polarization to and
from the cell membrane. This spatial separation of membrane and cytosol, not
possible to capture in 1D or 2D models, leads to marked differences of our
model from comparable lower-dimensional models.Comment: 31 pages, 7 figure
Your money or your life: Comparing judgements in trolley problems involving economic and emotional Harms, injury and death: Natalie gold et al
There is a long-standing debate in philosophy about whether it is morally permissible to harm one person in order to prevent a greater harm to others and, if not, what is the moral principle underlying the prohibition. Hypothetical moral dilemmas are used in order to probe moral intuitions. Philosophers use them to achieve a reflective equilibrium between intuitions and principles, psychologists to investigate moral decision-making processes. In the dilemmas, the harms that are traded off are almost always deaths. However, the moral principles and psychological processes are supposed to be broader than this, encompassing harms other than death. Further, if the standard pattern of intuitions is preserved in the domain of economic harm, then that would open up the possibility of studying behaviour in trolley problems using the tools of experimental economics. We report the results of two studies designed to test whether the standard patterns of intuitions are preserved when the domain and severity of harm are varied. Our findings show that the difference in moral intuitions between bystander and footbridge scenarios is replicated across different domains and levels of physical and non-physical harm, including economic harms
OtherāSacrificing Options
I argue that you can be permitted to discount the interests of your adversaries even though doing so would be impartially suboptimal. This means that, in addition to the kinds of moral options that the literature traditionally recognises, there exist what I call other-sacrificing options. I explore the idea that you cannot discount the interests of your adversaries as much as you can favour the interests of your intimates; if this is correct, then there is an asymmetry between negative partiality toward your adversaries and positive partiality toward your intimates
Mechano-sensing and cell migration: A 3D model approach
Cell migration is essential for tissue development in different physiological and pathological conditions. It is a complex process orchestrated by chemistry, biological factors, microstructure and surrounding mechanical properties. Focusing on the mechanical interactions, cells do not only exert forces on the matrix that surrounds them, but they also sense and react to mechanical cues in a process called mechano-sensing. Here, we hypothesize the involvement of mechano-sensing in the regulation of directional cell migration through a three-dimensional (3D) matrix. For this purpose, we develop a 3D numerical model of individual cell migration, which incorporates the mechano-sensing process of the cell as the main mechanism regulating its movement. Consistent with this hypothesis, we found that factors, such as substrate stiffness, boundary conditions and external forces, regulate specific and distinct cell movements
Analysis of nanoprobe penetration through a lipid bilayer
AbstractWith the rapid development of nanotechnology and biotechnology, nanoscale structures are increasingly used in cellular biology. However, the interface between artificial materials and a biological membrane is not well understood, and the harm caused by the interaction is poorly controlled. Here, we utilize the dissipative particle dynamics simulation method to study the interface when a nanoscale probe penetrates the cell membrane, and propose that an appropriate surface architecture can reduce the harm experienced by a cell membrane. The simulation shows that a hydrophilic probe generates a hydrophilic hole around the probe while a hydrophobic probe leads to a āT-junctionā state as some lipid molecules move toward the two ends of the probe. Both types of probe significantly disrupt lipid bilayer organization as reflected by the large variations in free energy associated with penetration of the membrane. Considering the hydrophilic/hydrophobic nature of the lipid bilayer, three other hydrophilic/hydrophobic patterns ā band pattern, axial pattern and random pattern ā are discussed to reduce the damage to the lipid membrane. Both the free energy analysis and simulation studies show that the axial pattern and the random pattern can both minimize the variations in free energy with correspondingly smaller adverse effects on membrane function. These results suggest that the axial pattern or random pattern nanoprobe generates a mild interaction with the biological membrane, which should be considered when designing nondestructive nanoscale structures
A study of external pneumatic compression for the prevention of deep venous thrombosis
Thesis. 1977. Ph.D.--Massachusetts Institute of Technology. Dept. of Mechanical Engineering.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING.Vita.Bibliography: p. 200-205.by Roger D. Kamm.Ph.D
In vitro models of molecular and nano-particle transport across the blood-brain barrier
The blood-brain barrier (BBB) is the tightest endothelial barrier in humans.
Characterized by the presence of tight endothelial junctions and adherens junctions,
the primary function of the BBB is to maintain brain homeostasis through
the control of solute transit across the barrier. The specific features of this barrier
make for unique modes of transport of solutes, nanoparticles, and cells across the
BBB. Understanding the different routes of traffic adopted by each of these is
therefore critical in the development of targeted therapies. In an attempt to move
towards controlled experimental assays, multiple groups are now opting for the
use of microfluidic systems. A comprehensive understanding of bio-transport processes
across the BBB in microfluidic devices is therefore necessary to develop
targeted and efficient therapies for a host of diseases ranging from neurological
disorders to the spread of metastases in the brain
In Vitro Microfluidic Models for Neurodegenerative Disorders
Microfluidic devices enable novel means of emulating neurodegenerative
disease pathophysiology in vitro. These organ-on-a-chip systems can potentially
reduce animal testing and substitute (or augment) simple 2D culture
systems. Reconstituting critical features of neurodegenerative diseases in a
biomimetic system using microfluidics can thereby accelerate drug discovery
and improve our understanding of the mechanisms of several currently incurable
diseases. This review describes latest advances in modeling neurodegenerative
diseases in the central nervous system and the peripheral nervous
system. First, this study summarizes fundamental advantages of microfluidic
devices in the creation of compartmentalized cell culture microenvironments
for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle
cells and in their recapitulation of spatiotemporal chemical gradients and
mechanical microenvironments. Then, this reviews neurodegenerative-disease-
on-a-chip models focusing on Alzheimerās disease, Parkinsonās disease,
and amyotrophic lateral sclerosis. Finally, this study discusses about current
drawbacks of these models and strategies that may overcome them. These
organ-on-chip technologies can be useful to be the first line of testing line in
drug development and toxicology studies, which can contribute significantly
to minimize the phase of animal testing steps
Morphological Transformation and Force Generation of Active Cytoskeletal Networks
Cells assemble numerous types of actomyosin bundles that generate contractile forces for biological processes, such as cytokinesis and cell migration. One example of contractile bundles is a transverse arc that forms via actomyosin-driven condensation of actin filaments in the lamellipodia of migrating cells and exerts significant forces on the surrounding environments. Structural reorganization of a network into a bundle facilitated by actomyosin contractility is a physiologically relevant and biophysically interesting process. Nevertheless, it remains elusive how actin filaments are reoriented, buckled, and bundled as well as undergo tension buildup during the structural reorganization. In this study, using an agent-based computational model, we demonstrated how the interplay between the density of myosin motors and cross-linking proteins and the rigidity, initial orientation, and turnover of actin filaments regulates the morphological transformation of a cross-linked actomyosin network into a bundle and the buildup of tension occurring during the transformation
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