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The theoretical framework of conventional contact mechanics is based on idealized as- sumptions that have shaped the field for more than 140 years. Unfortunately, these assumptions do not lend themselves to the modelling of thin films, viscoelastic materials and frictional interfaces. Therefore, the present thesis is concerned with the system- atic generalization of these assumptions and their GFMD implementation to simulate a variety of previously inaccessible, realistic contact problems. First, finite material thickness is considered in the design of film-terminated fibril struc- tures for skin adhesion. An elastic film resting on a hard foundation is effectively more stiff than its bulk counterpart, which reduces its ability to conform to counter-faces and therefore reduces the adhesion to roughness. Second, the velocity-dependence of soft, adhesive multi-asperity contacts is studied, revealing the importance of topographical saddle points and the initial configuration, from which detachment is initiated. Further- more, we identify a scaling relation describing how short-ranged microscopic interactions slow down the macroscopic relaxation of a contact. Finally, we explore the influence of interfacial friction, showing that it increases local stress concentrations and impedes the fluid flow through the interface. The reported results provide new insight into commonly neglected phenomena, whose practical significance is reinforced by direct comparisons to experiments.
NK cells are one of the major immune killer cell types exhibiting anti-tumor activity. During immune surveillance NK cells infiltrate into tissues and come in contact with cells and organs with varied stiffness. It has been shown that tumor cells with a lower elasticity modulus than their counterparts to have a higher metastatic potential. Whether the change in tumor cell stiffness affects the functionality of NK cells is not well understood. In this work, to test the effect of substrate stiffness on NK responses, PAAm-co-AA hydrogels of varied stiffness (2 kPa,12 kPa, 50 kPa) functionalized with biotinylated NKp46 activating antibody, prepared by Dr. Jingnan Zhang (research group of Prof. del Campo, INM-Leibniz Institute for New Materials) were used. Stiffness of substrate indeed played a huge role in modulating NK responses with stiffer substrates (12 kPa, 50 kPa) eliciting a stronger response in most donors whereas the soft substrates (2 kPa) failed to do so. To further test the impact of target cell stiffness on NK cytolytic activity, stiffness of target cells was altered using blebbistatin (made cells stiffer) and DMSO (made cells softer). Cytotoxicity of NK cells was boosted against stiffened tumor cells and impaired against softened tumor cells. In addition, the time required for NK cell to detach from the stiffened target cell after apoptosis or necrosis of the latter was significantly shorter, also contributing to a more effective cytotoxicity. To further decipher the role of mechanosensing in killing processes, functions of mechanosensitive ion channels was blocked using unspecific antagonizers (gadolinium and nifedipine), and it was found that blockage of mechanosensing substantially impaired NK mediated cytotoxicity as determined by 2D and 3D killing assays. Regarding the responsible mechanosensor, we have identified from the microarray data of our lab (by Dr. Eva Schwarz) that PIEZO1 are the predominately expressed mechanosensitive ion channels in NK cells. Blockade of PIEZO1 in NK cells by GsMTx4 impaired NK mediated cytotoxicity and activation of PIEZO1, using its specific agonist Yoda-1, potentiated NK mediated killing of the target cells. Blockade of PIEZO1 was shown to decrease the infiltration of NK cells into 3D collagen matrices, and activation of PIEZO1 boosted the infiltration of NK cells into 3D collagen matrix. As the role of PIEZO1 to be a major mechanosensor in NK cells was established, its role in sensing the stiffness of substrates was explored. Perturbation of PIEZO1 channels abrogated NK responses to substrate stiffness. Together, these data emphasize the role of mechanosensing in regulating NK cytotoxicity and the central role of tumor cell stiffness in evading immune surveillance. To fight cancer and other infective diseases, living therapeutic materials (LTMs) offer possibilities to release therapeutics in a sustainable and tunable manner. LTMs contain genetically engineered biological component encapsulated in a polymeric material such as hydrogels to contain their exposure in the host. LTMs are being extensively researched for their use in treatment of cancer with many studies reinforcing the beneficial effects of using smart materials. To contain the exposure of living component such as bacteria and to protect it from adverse environmental conditions of the host and to avoid a direct contact with immune cells, they are often encapsulated. However, one major concern for LTMs is that they may trigger an immune response and create a pro-inflammatory milieu in the host which could lead to critical situations if unregulated. So, the second part of my thesis is to characterize the immune response of PBMCs to PluDA hydrogel encapsulated E.coli and ClearColi bacteria. This work was carried out in collaboration with the group of Dr. Shrikrishnan Sankaran, Bioprogramable materials, INM-Leibniz Institute for New Materials, Saarbrücken. The ClearColi strain was produced from E.coli after genetically deleting LPS. ClearColi was encapsulated in Pluronic F127-based hydrogels (PluDA). It has to be noted that the bacteria were not in direct contact with the host so any immune reaction elicited would be due to the release of soluble factors and metabolites. The release of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNFα and IFNγ) and cytotoxic proteins (granzyme A, granzyme B, perforin, granulysin, sFas, and sFasL) by PBMCs in response to bacteria and bacteria encapsulated gels was checked along with its influence on immune killer cells’ subtypes. Interestingly, PBMCs from the blood donors could be grouped in to two groups, donors with low spontaneous IL-2 and high spontaneous IL-2 release, based on the IL-2 release when PBMCs were cultured alone. Our results show that co-incubation of PluDA blank gels with PBMCs did not alter their profiles of cytokines and cytotoxic proteins, and had no influence on differentiation of NK cells, CD4+ and CD8+ T cells in donors with low spontaneous release of IL-2. ClearColi elicited release of IL-6 and IFNγ from PBMCs. Interestingly, the predominantly released cytokine was IL-6 for low spontaneous IL-2 release donors, but IFNγ for high spontaneous IL-2 release donors. Both the transwell condition and the encapsulated gel condition showed the same tendency. When the bacteria were in direct contact with the PBMCs they triggered the apoptosis of PBMCs on day 3 but encapsulation of the bacteria in PluDA gels completely abolished this effect.
Search processes often involve multiple agents that collectively look for a randomly located target. While increasing the number of agents usually decreases the time at which the first agent finds the target, it also requires resources to create and sustain more agents. In this letter, we consider a collective search cost that not only accounts for the search time but also for the cost associated to the creation and the maintenance of an agent. We first present a general formalism for independent agents in terms of the survival probability of the target for a single-agent search s(t), where we allow agents to be introduced in the system one after the other. From this, we first derive analytically the optimal number of searchers to launch initially in the system. Then, we identify the optimal strategies for exponential and algebraic single-agent survival probabilities by pointing out the ideal times at which new searchers should be launched in the system. Our results show that all searchers should be launched simultaneously in the exponential case, while some should be launched at later times in the algebraic case. Finally, we compare these results with numerical simulations of a strongly interacting collective search, the true self-avoiding walk, and show how the optimal strategy differ from the non-interacting case.
We undertake a numerical study of the ordering kinetics in the two-dimensional (2d) active Ising model (AIM), a discrete flocking model with a non-conserved scalar order parameter. We find that for a quench into the liquid-gas coexistence region and in the ordered liquid region, the characteristic length scale of both the density and magnetization domains follows the Lifshitz-Cahn-Allen (LCA) growth law: R(t)∼t1/2, consistent with the growth law of passive systems with scalar order parameter and non-conserved dynamics. The system morphology is analyzed with the two-point correlation function and its Fourier transform, the structure factor, which conforms to the well-known Porod's law, a manifestation of the coarsening of compact domains with smooth boundaries. We also find the domain growth exponent unaffected by different noise strengths and self-propulsion velocities of the active particles. However, transverse diffusion is found to play the most significant role in the growth kinetics of the AIM. We extract the same growth exponent by solving the hydrodynamic equations of the AIM.
We numerically study a discretized Vicsek model (DVM) with particles orienting in q possible orientations in two dimensions. The study probes the significance of anisotropic orientation and microscopic interaction on the macroscopic behavior. The DVM is an off-lattice flocking model like the active clock model [ACM; EPL {\bf 138}, 41001 (2022)] but the dynamical rules of particle alignment and movement are inspired by the prototypical Vicsek model (VM). The DVM shows qualitatively similar properties as the ACM for intermediate noise strength where a transition from macrophase to microphase separation of the coexistence region is observed as q is increased. But for small q and noise strength, the liquid phase appearing in the ACM at low temperatures is replaced in the DVM by a configuration of multiple clusters with different polarization which does not exhibit any long-range order. We find that the dynamical rules have a profound influence on the overarching features of the flocking phase. We further identify the metastability of the ordered liquid phase subjected to a perturbation.
We numerically study a discretized Vicsek model (DVM) with particles orienting in q possible orientations in two dimensions. The study probes the significance of anisotropic orientation and microscopic interaction on the macroscopic behavior. The DVM is an off-lattice flocking model like the active clock model [ACM; EPL {\bf 138}, 41001 (2022)] but the dynamical rules of particle alignment and movement are inspired by the prototypical Vicsek model (VM). The DVM shows qualitatively similar properties as the ACM for intermediate noise strength where a transition from macrophase to microphase separation of the coexistence region is observed as q is increased. But for small q and noise strength, the liquid phase appearing in the ACM at low temperatures is replaced in the DVM by a configuration of multiple clusters with different polarization which does not exhibit any long-range order. We find that the dynamical rules have a profound influence on the overarching features of the flocking phase. We further identify the metastability of the ordered liquid phase subjected to a perturbation.
We numerically study a discretized Vicsek model (DVM) with particles orienting in q possible orientations in two dimensions. The study investigates the significance of anisotropic orientation and microscopic interaction on macroscopic behavior. The DVM is an off-lattice flocking model like the active clock model (ACM; Chatterjee et al 2022 Europhys. Lett.138 41001) but the dynamical rules of particle alignment and movement are inspired by the prototypical Vicsek model (VM). The DVM shows qualitatively similar properties as the ACM for intermediate noise strength where a transition from macrophase to microphase separation of the coexistence region is observed as q is increased. But for small q and noise strength, the liquid phase appearing in the ACM at low temperatures is replaced in the DVM by a configuration of multiple clusters with different polarizations, which does not exhibit any long-range order. We find that the dynamical rules have a profound influence on the overarching features of the flocking phase. We further identify the metastability of the ordered liquid phase subjected to a perturbation.
Many biological active agents respond to gradients of environmental cues by redirecting their motion. In addition to the well-studied prominent examples such as phototaxis and chemotaxis, there has been considerable recent interest in topotaxis, i.e., the ability to sense and follow topographic environmental cues. A trivial topotaxis is achievable through a spatial gradient of obstacle density, though over limited length scales. Here, we introduce a type of topotaxis based on sliding of particles along obstacles—as observed, e.g., in bacterial dynamics near surfaces. We numerically demonstrate how imposing a gradient in the angle of sliding along pillars breaks the spatial symmetry and biases the direction of motion, resulting in an efficient topotaxis in a uniform pillar park. By repeating blocks of pillars with a strong gradient of sliding angle, we propose an efficient method for guiding particles over arbitrary long distances. We provide an explanation for this spectacular phenomenon based on effective reflection at the borders of neighboring blocks. Our results are of technological and medical importance for design of efficient taxis devices for living agents.
An important challenge in active matter lies in harnessing useful global work from entities that produce work locally, e.g., via self-propulsion. We investigate here the active matter version of a classical capillary rise effect, by considering a non-phase separated sediment of self-propelled Janus colloids in contact with a vertical wall. We provide experimental evidence of an unexpected and dynamic adsorption layer at the wall. Additionally, we develop a complementary numerical model that recapitulates the experimental observations. We show that an adhesive and aligning wall enhances the pre-existing polarity heterogeneity within the bulk, enabling polar active particles to climb up a wall against gravity, effectively powering a global flux. Such steady-state flux has no equivalent in a passive wetting layer.
Agents searching for a target can improve their efficiency by memorizing where they have already been searching or by cooperating with other searchers and using strategies that benefit from collective effects. This chapter reviews such concepts: non-Markovian and collective search strategies. We start with the first passage properties of continuous non-Markovian processes and then proceed to the discrete random walker with 1-step and n-step memory. Next we discuss the auto-chemotactic walker, a random walker that produces a diffusive chemotactic cue from which the walker tries to avoid. Then ensembles of agents searching for a single target are discussed, whence the search efficiency may comprise in addition to the first passage time also metabolic costs. We consider the first passage properties of ensembles of chemotactic random walkers and then the pursuit problem, in which searchers (or hunters / predators) see the mobile target over a certain distance. Evasion strategies of single or many targets are also elucidated. Finally we review collective foraging strategies comprising many searchers and many immobile targets. We finish with an outlook on future research directions comprising yet unexplored search strategies of immune cells and in swarm robotics.
