108 research outputs found
Jamming transitions in cancer
The traditional picture of tissues, where they are treated as liquids defined by properties such
as surface tension or viscosity has been redefined during the last few decades by the more
fundamental question: under which conditions do tissues display liquid-like or solid-like
behaviour? As a result, basic concepts arising from the treatment of tissues as solid matter,
such as cellular jamming and glassy tissues, have shifted into the current focus of biophysical
research. Here, we review recent works examining the phase states of tissue with an emphasis
on jamming transitions in cancer. When metastasis occurs, cells gain the ability to leave the
primary tumour and infiltrate other parts of the body. Recent studies have shown that a linkage
between an unjamming transition and tumour progression indeed exists, which could be of
importance when designing surgery and treatment approaches for cancer patient
Jamming in Embryogenesis and Cancer Progression
The ability of tissues and cells to move and rearrange is central to a broad range of diverse
biological processes such as tissue remodeling and rearrangement in embryogenesis, cell
migration in wound healing, or cancer progression. These processes are linked to a solidlike
to fluid-like transition, also known as unjamming transition, a not rigorously defined
framework that describes switching between a stable, resting state and an active, moving
state. Various mechanisms, that is, proliferation and motility, are critical drivers for the (un)
jamming transition on the cellular scale. However, beyond the scope of these fundamental
mechanisms of cells, a unifying understanding remains to be established. During
embryogenesis, the proliferation rate of cells is high, and the number density is
continuously increasing, which indicates number-density-driven jamming. In contrast,
cells have to unjam in tissues that are already densely packed during tumor
progression, pointing toward a shape-driven unjamming transition. Here, we review
recent investigations of jamming transitions during embryogenesis and cancer
progression and pursue the question of how they might be interlinked. We discuss the
role of density and shape during the jamming transition and the different biological factors
driving it
Stages of neuronal network formation
Graph theoretical approaches have become a powerful tool for
investigating the architecture and dynamics of complex networks. The topology
of network graphs revealed small-world properties for very different real
systems among these neuronal networks. In this study, we observed the early
development of mouse retinal ganglion cell (RGC) networks in vitro using timelapse
video microscopy. By means of a time-resolved graph theoretical analysis
of the connectivity, shortest path length and the edge length, we were able to
discover the different stages during the network formation. Starting from single
cells, at the first stage neurons connected to each other ending up in a network
with maximum complexity. In the further course, we observed a simplification of
the network which manifested in a change of relevant network parameters such
as the minimization of the path length. Moreover, we found that RGC networks
self-organized as small-world networks at both stages; however, the optimization
occurred only in the second stage
Thermorheology of living cells: impact of temperature variations on cell mechanics
Upon temperature changes, we observe a systematic shift of creep
compliance curves J (t) for single living breast epithelial cells. We use a
dual-beam laser trap (optical stretcher) to induce temperature jumps within
milliseconds, while simultaneously measuring the mechanical response of whole
cells to optical force. The cellular mechanical response was found to differ
between sudden temperature changes compared to slow, long-term changes
implying adaptation of cytoskeletal structure. Interpreting optically induced cell
deformation as a thermorheological experiment allows us to consistently explain
data on the basis of time–temperature superposition, well known from classical
polymer physics. Measured time shift factors give access to the activation
energy of the viscous flow of MCF-10A breast cells, which was determined
to be 80 kJ mol−1. The presented measurements highlight the fundamental
role that temperature plays for the deformability of cellular matter. We propose
thermorheology as a powerful concept to assess the inherent material properties
of living cells and to investigate cell regulatory responses upon environmental
changes
Oscillations in the Lateral Pressure of Lipid Monolayers Induced by Nonlinear Chemical Dynamics of the Second Messengers MARCKS and Protein Kinase C
AbstractThe binding of the MARCKS peptide to the lipid monolayer containing PIP2 increases the lateral pressure of the monolayer. The unbinding dynamics modulated by protein kinase C leads to oscillations in lateral pressure of lipid monolayers. These periodic dynamics can be attributed to changes in the crystalline lipid domain size. We have developed a mathematical model to explain these observations based on the changes in the physical structure of the monolayer by the translocation of MARCKS peptide. The model indicates that changes in lipid domain size drives these oscillations. The model is extended to an open system that sustains chemical oscillations
The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients
Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection
Anomalous cell sorting behavior in mixed monolayers discloses hidden system complexities
In tissue development, wound healing and aberrant cancer progression cell–cell interactions drive
mixing and segregation of cellular composites. However, the exact nature of these interactions is
unsettled. Here we study the dynamics of packed, heterogeneous cellular systems using wound
closure experiments. In contrast to previous cell sorting experiments, we find non-universal
sorting behavior. For example, monolayer tissue composites with two distinct cell types that show
low and high neighbor exchange rates (i.e., MCF-10A & MDA-MB-231) produce segregated
domains of each cell type, contrary to conventional expectation that the construct should stay
jammed in its initial configuration. On the other hand, tissue compounds where both cell types
exhibit high neighbor exchange rates (i.e., MDA-MB-231 & MDA-MB-436) produce highly mixed
arrangements despite their differences in intercellular adhesion strength. The anomalies allude to a
complex multi-parameter space underlying these sorting dynamics, which remains elusive in
simpler systems and theories merely focusing on bulk properties. Using cell tracking data, velocity
profiles, neighborhood volatility, and computational modeling, we classify asymmetric interfacial
dynamics. We indicate certain understudied facets, such as the effects of cell death & division,
mechanical hindrance, active nematic behavior, and laminar & turbulent flow as their potential
drivers. Our findings suggest that further analysis and an update of theoretical models, to capture
the diverse range of active boundary dynamics which potentially influence self-organization, is
warranted
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