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Abstract Immune cells, such as macrophages and dendritic cells, can utilize podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.
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Distributed Network of Coupled Oscillators With Multiple Limit Cycles
When designing feedback controllers to achieve periodic movements, a reference trajectory generator for oscillations is an important component. Using autonomous oscillators to this effect, rather than directly crafting periodic signals, may allow for systematic coordination in a distributed manner and storage of multiple motion patterns within the nonlinear dynamics, with potential extensions to adaptive mode switching through sensory feedback. This paper proposes a method for designing a distributed network that possesses multiple stable limit cycles from which various output patterns are generated with prescribed frequency, amplitude, temporal shapes, and phase coordination. In particular, we adopt, as the basic dynamical unit, a simple nonlinear oscillator with a scalar complex state variable, and derive conditions for their distributed interconnections to result in a network that embeds desired periodic solutions with orbital stability. We show that the frequencies and phases of target oscillations are encoded into the network connectivity matrix as its eigenvalues and eigenvectors, respectively. Various design examples will illustrate the proposed method, including generation of human gaits for walking and running.
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- Award ID(s):
- 2113528
- PAR ID:
- 10552122
- Publisher / Repository:
- IEEE
- Date Published:
- Journal Name:
- IEEE Transactions on Automatic Control
- Volume:
- 69
- Issue:
- 5
- ISSN:
- 0018-9286
- Page Range / eLocation ID:
- 3112 - 3127
- Subject(s) / Keyword(s):
- Nonlinear oscillator distributed network multistability limit cycles gait generation
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1109/TAC.2023.3334081
