Optical tweezers (OT) have emerged as an essential tool for manipulating single biological cells and performing sophisticated biophysical/biomechanical characterizations. Distinct advantages of using tweezers for these characterizations include non-contact force for cell manipulation, force resolution as accurate as 100 aN and amiability to liquid medium environments. Their wide range of applications, such as transporting foreign materials into single cells, delivering cells to specific locations and sorting cells in microfluidic systems, are reviewed in this article. Recent developments of OT for nanomechanical characterization of various biological cells are discussed in terms of both their theoretical and experimental advancements. The future trends of employing OT in single cells, especially in stem cell delivery, tissue engineering and regenerative medicine, are prospected. More importantly, current limitations and future challenges of OT for these new paradigms are also highlighted in this review.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2008.0052

Optical tweezers for single cells

Close to a transition between different phases a substance can show universal behavior that is independent of the microscopic details and is characterized by power law correlations and critical exponents. In this Colloquium the concepts of criticality and universality are discussed when applied to biological systems and suggest that in some cases these systems can extract functional advantages close to criticality.

Colloquium : Criticality and dynamical scaling in living systems

Swimming microrobots that are energized by external magnetic fields exhibit a variety of intriguing collective behaviors, ranging from dynamic self-organization to coherent motion; however, achieving multiple, desired collective modes within one colloidal system to emulate high environmental adaptability and enhanced tasking capabilities of natural swarms is challenging. Here, we present a strategy that uses alternating magnetic fields to program hematite colloidal particles into liquid, chain, vortex, and ribbon-like microrobotic swarms and enables fast and reversible transformations between them. The chain is characterized by passing through confined narrow channels, and the herring school-like ribbon procession is capable of large-area synchronized manipulation, whereas the colony-like vortex can aggregate at a high density toward coordinated handling of heavy loads. Using the developed discrete particle simulation methods, we investigated generation mechanisms of these four swarms, as well as the "tank-treading" motion of the chain and vortex merging. In addition, the swarms can be programmed to steer in any direction with excellent maneuverability, and the vortex's chirality can be rapidly switched with high pattern stability. This reconfigurable microrobot swarm can provide versatile collective modes to address environmental variations or multitasking requirements; it has potential to investigate fundamentals in living systems and to serve as a functional bio-microrobot system for biomedicine.

Reconfigurable magnetic microrobot swarm: Multimode transformation, locomotion, and manipulation.

Active colloids exhibit persistent motion, which can lead to motility-induced phase separation (MIPS). However, there currently exists no microscopic theory to account for this phenomenon. We report a first-principles theory, free of fit parameters, for active spherical colloids, which shows explicitly how an effective many-body interaction potential is generated by activity and how this can rationalize MIPS. For a passively repulsive system the theory predicts phase separation and pair correlations in quantitative agreement with simulation. For an attractive system the theory shows that phase separation becomes suppressed by moderate activity, consistent with recent experiments and simulations, and suggests a mechanism for reentrant cluster formation at high activity.

/pdf/effective-interactions-in-active-brownian-suspensions-3nttfb039c.pdf

Effective interactions in active Brownian suspensions.

We describe here a rigorous and accurate model for the simulation of three-dimensional deformable particles (DPs). The method is very versatile, easily simulating various types of deformable particles such as vesicles, capsules, and biological cells. Each DP is resolved explicitly and advects within the surrounding Newtonian fluid. The DPs have a preferred rest shape (e.g., spherical for vesicles, or biconcave for red blood cells). The model uses a classic hybrid system: an Eulerian approach is used for the Navier-Stokes solver (the lattice Boltzmann method) and a Lagrangian approach for the evolution of the DP mesh. Coupling is accomplished through the lattice Boltzmann velocity field, which transmits force to the membranes of the DPs. The novelty of this method resides in its ability (by design) to simulate a large number of DPs within the bounds of current computational limitations: our simple and efficient approach is to (i) use the lattice Boltzmann method because of its acknowledged efficiency at low Reynolds number and its ease of parallelization, and (ii) model the DP dynamics using a coarse mesh (approximately 500 nodes) and a spring model constraining (if necessary) local area, total area, cell volume, local curvature, and local primary stresses. We show that this approach is comparable to the more common - yet numerically expensive - approach of membrane potential function, through a series of quantitative comparisons. To demonstrate the capabilities of the model, we simulate the flow of 200 densely packed red blood cells - a computationally challenging task. The model is very efficient, requiring of the order of minutes for a single DP in a 50 microm x 40 microm x 40 microm simulation domain and only hours for 200 DPs in 80 microm x 30 microm x 30 microm . Moreover, the model is highly scalable and efficient compared to other models of blood cells in flow, making it an ideal and unique tool for studying blood flow in microvessels or vesicle or capsule flow (or a mixture of different particles). In addition to directly predicting fluid dynamics in complex suspension in any geometry, the model allows determination of accurate, empirical rules which may improve existing macroscopic, continuum models.

/pdf/modeling-the-flow-of-dense-suspensions-of-deformable-yof8x55iwm.pdf

Modeling the flow of dense suspensions of deformable particles in three dimensions.

To cooperatively transport a large load, it is important that carriers conform in their efforts and align their forces. A downside of behavioural conformism is that it may decrease the group's responsiveness to external information. Combining experiment and theory, we show how ants optimize collective transport. On the single-ant scale, optimization stems from decision rules that balance individuality and compliance. Macroscopically, these rules poise the system at the transition between random walk and ballistic motion where the collective response to the steering of a single informed ant is maximized. We relate this peak in response to the divergence of susceptibility at a phase transition. Our theoretical models predict that the ant-load system can be transitioned through the critical point of this mesoscopic system by varying its size; we present experiments supporting these predictions. Our findings show that efficient group-level processes can arise from transient amplification of individual-based knowledge.

/pdf/ant-groups-optimally-amplify-the-effect-of-transiently-qk5spp8t3d.pdf

Ant groups optimally amplify the effect of transiently informed individuals

https://www.cell.com/biophysj/pdf/S0006-3495(14)00779-6.pdf

Dynamics of Active Semiflexible Polymers

We investigate the physics of an optically driven micromotor of biological origin. When a single, live red blood cell (RBC) is placed in an optical trap, the normal biconcave disc shape of the cell is observed to fold into a rod-like shape. If the trapping laser beam is circularly polarized, the folded RBC rotates. A model based on geometric considerations, using the concept of buckling instabilities, captures the folding phenomenon; the rotation of the cell is rationalized using the Poincare sphere. Our model predicts that (i) at a critical power of the trapping laser beam the RBC shape undergoes large fluctuations, and (ii) the torque that is generated is proportional to the power of the laser beam. These predictions are verified experimentally. We suggest a possible mechanism for the emergence of birefringent properties in the RBC in the folded state.

https://iopscience.iop.org/article/10.1088/1478-3975/3/1/007/pdf

Euler buckling-induced folding and rotation of red blood cells in an optical trap

We present an analytical closed form expression, which gives a good approximate propagator for diffusion on the sphere. Our formula is the spherical counterpart of the Gaussian propagator for diffusion on the plane. While the analytical formula is derived using saddle point methods for short times, it works well even for intermediate times. Our formula goes beyond conventional "short time heat kernel expansions" in that it is nonperturbative in the spatial coordinate, a feature that is ideal for studying large deviations. Our work suggests a new and efficient algorithm for numerical integration of the diffusion equation on a sphere. We perform Monte Carlo simulations to compare the numerical efficiency of the new algorithm with the older Gaussian one.

A “Gaussian” for diffusion on the sphere

We consider the thermal breakage of a tethered polymer chain of discrete segments coupled by Morse potentials under constant tensile stress. The chain dynamics at the onset of fracture is studied analytically by Kramers-Langer multidimensional theory and by extensive molecular dynamics simulations in one dimension (1D) and three dimension (3D) space. Comparison with simulation data in one and three dimensions demonstrates that the Kramers-Langer theory provides good qualitative description of the process of bond scission as caused by a collective unstable mode. We derive distributions of the probability for scission over the successive bonds along the chain which reveal the influence of chain ends on rupture in good agreement with theory. The breakage time distribution of an individual bond is found to follow an exponential law as predicted by theory. Special attention is focused on the recombination (self-healing) of broken bonds. Theoretically derived expressions for the recombination time and distance distributions comply with MD observations and indicate that the energy barrier position crossing is not a good criterion for true rupture. It is shown that the fraction of self-healing bonds increases with rising temperature and friction.

Abhijit Ghosh

Papers

Ant groups optimally amplify the effect of transiently informed individuals

Dynamics of Active Semiflexible Polymers

Euler buckling-induced folding and rotation of red blood cells in an optical trap

A “Gaussian” for diffusion on the sphere

Thermal breakage and self-healing of a polymer chain under tensile stress.