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Nicholas A. Licata

Publications and source records attributed to Nicholas A. Licata.

13 recordsLinked to original sources

The Chemotactic Index for Spatial Gradient Sensing

We consider the problem of quantifying the chemotactic efficiency of single cells as measured by the chemotactic index $Ψ$. Previous work in a model framework for direct sensing of spatial gradients indicated that $Ψ$ depends on a single dimensionless group $s$, which plays the role of the square of the signal to noise ratio in the problem. We revisit this problem theoretically and demonstrate that the cumulants in the model can be calculated exactly. We derive explicit results for the multivariate cumulants up to third order in terms of the diffusive current density and Gaunt coefficients. We discuss the machinery required to translate Burg-Purcell style limits on concentration gradient uncertainty into results for the chemotactic index. We compute the leading corrections to $Ψ$ in an Edgeworth expansion, and identify a dimensionless group $λ$ in the problem which is a ratio of concentrations that captures the effects of the non-Gaussianity. By careful consideration of experimental results on slime mold chemotaxis, we demonstrate that the explanatory success of the original Gaussian approximation for the chemotactic index stems in part from the fact the concentration gradients were shallow, $|λ| \ll s$.

physics.bio-ph

Numerical and analytical approaches to an advection-diffusion problem at small Reynolds number and large Péclet number

Obtaining a detailed understanding of the physical interactions between a cell and its environment often requires information about the flow of fluid surrounding the cell. Cells must be able to effectively absorb and discard material in order to survive. Strategies for nutrient acquisition and toxin disposal, which have been evolutionarily selected for their efficacy, should reflect knowledge of the physics underlying this mass transport problem. Motivated by these considerations, in this paper we discuss the results from an undergraduate research project on the advection-diffusion equation at small Reynolds number and large Péclet number. In particular, we consider the problem of mass transport for a Stokesian spherical swimmer. We approach the problem numerically and analytically through a rescaling of the concentration boundary layer. A biophysically motivated first-passage problem for the absorption of material by the swimming cell demonstrates quantitative agreement between the numerical and analytical approaches. We conclude by discussing the connections between our results and the design of smart toxin disposal systems.

physics.bio-ph

Fluid flow enhances the effectiveness of toxin export by aquatic microorganisms: a first-passage perspective on microvilli and the concentration boundary layer

A central challenge for organisms during development is determining a means to efficiently export toxic molecules from inside the developing embryo. For aquatic microorganisms, the strategies employed should be robust with respect to the variable ocean environment and limit the chances that exported toxins are reabsorbed. As a result, the problem of toxin export is closely related to the physics of mass transport in a fluid. In this paper we consider a model first-passage problem for the uptake of exported toxins by a spherical embryo. By considering how macroscale fluid turbulence manifests itself on the microscale of the embryo, we determine that fluid flow enhances the effectiveness of toxin export as compared to the case of diffusion-limited transport. In the regime of large Péclet number, a perturbative solution of the advection-diffusion equation reveals that a concentration boundary layer forms at the surface of the embryo. The model results suggest a functional role for cell surface roughness in the export process, with the thickness of the concentration boundary layer setting the length scale for cell membrane protrusions known as microvilli. We highlight connections between the model results and experiments on the development of sea urchin embryos.

physics.bio-ph

The first passage problem for diffusion through a cylindrical pore with sticky walls

We calculate the first passage time distribution for diffusion through a cylindrical pore with sticky walls. A particle diffusively explores the interior of the pore through a series of binding and unbinding events with the cylinder wall. Through a diagrammatic expansion we obtain first passage time statistics for the particle's exit from the pore. Connections between the model and nucleocytoplasmic transport in cells are discussed.

cond-mat.soft

Self-assembling DNA-caged particles: nanoblocks for hierarchical self-assembly

DNA is an ideal candidate to organize matter on the nanoscale, primarily due to the specificity and complexity of DNA based interactions. Recent advances in this direction include the self-assembly of colloidal crystals using DNA grafted particles. In this article we theoretically study the self-assembly of DNA-caged particles. These nanoblocks combine DNA grafted particles with more complicated purely DNA based constructs. Geometrically the nanoblock is a sphere (DNA grafted particle) inscribed inside a polyhedron (DNA cage). The faces of the DNA cage are open, and the edges are made from double stranded DNA. The cage vertices are modified DNA junctions. We calculate the equilibriuim yield of self-assembled, tetrahedrally caged particles, and discuss their stability with respect to alternative structures. The experimental feasability of the method is discussed. To conclude we indicate the usefulness of DNA-caged particles as nanoblocks in a hierarchical self-assembly strategy.

cond-mat.soft

How to build nanoblocks using DNA scaffolds

In recent years there have been a number of proposals to utilize the specificity of DNA based interactions for potential applications in nanoscience. One interesting direction is the self-assembly of micro- and nanoparticle clusters using DNA scaffolds. In this letter we consider a DNA scaffold method to self-assemble clusters of "colored" particles. Stable clusters of microspheres have recently been produced by an entirely different method. Our DNA based approach self-assembles clusters with additional degrees of freedom associated with particle permutation. We demonstrate that in the non-equilibrium regime of irreversible binding the self-assembly process is experimentally feasible. These color degrees of freedom may allow for more diverse intercluster interactions essential for hierarchical self-assembly of larger structures.

cond-mat.soft

Theory and modeling of particles with DNA-mediated interactions

In recent years significant attention has been attracted to proposals which utilize DNA for nanotechnological applications. Potential applications of these ideas range from the programmable self-assembly of colloidal crystals, to biosensors and nanoparticle based drug delivery platforms. In Chapter I we introduce the system, which generically consists of colloidal particles functionalized with specially designed DNA markers. The sequence of bases on the DNA markers determines the particle type. Due to the hybridization between complementary single-stranded DNA, specific, type-dependent interactions can be introduced between particles by choosing the appropriate DNA marker sequences. In Chapter II we develop a statistical mechanical description of the aggregation and melting behavior of particles with DNA-mediated interactions. In Chapter III a model is proposed to describe the dynamical departure and diffusion of particles which form reversible key-lock connections. In Chapter IV we propose a method to self-assemble nanoparticle clusters using DNA scaffolds. A natural extension is discussed in Chapter V, the programmable self-assembly of nanoparticle clusters where the desired cluster geometry is encoded using DNA-mediated interactions. In Chapter VI we consider a nanoparticle based drug delivery platform for targeted, cell specific chemotherapy. In Chapter VII we present prospects for future research: the connection between DNA-mediated colloidal crystallization and jamming, and the inverse problem in self-assembly.

cond-mat.soft

Kinetic limitations of cooperativity based drug delivery systems

We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in-vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea. The implications of the work for optimizing the design of drug delivery vehicles are discussed.

cond-mat.soft

Colloids with key-lock interactions: non-exponential relaxation, aging and anomalous diffusion

The dynamics of particles interacting by key-lock binding of attached biomolecules are studied theoretically. Experimental realizations of such systems include colloids grafted with complementary single-stranded DNA (ssDNA), and particles grafted with antibodies to cell-membrane proteins. Depending on the coverage of the functional groups, we predict two distinct regimes. In the low coverage localized regime, there is an exponential distribution of departure times. As the coverage is increased the system enters a diffusive regime resulting from the interplay of particle desorption and diffusion. This interplay leads to much longer bound state lifetimes, a phenomenon qualitatively similar to aging in glassy systems. The diffusion behavior is analogous to dispersive transport in disordered semiconductors: depending on the interaction parameters it may range from a finite renormalization of the diffusion coefficient to anomalous, subdiffusive behavior. We make connections to recent experiments and discuss the implications for future studies.

cond-mat.soft

Self-assembly of DNA-coded nanoclusters

We present a theoretical discussion of a self-assembly scheme which makes it possible to use DNA to uniquely encode the composition and structure of micro- and nanoparticle clusters. These anisotropic DNA-decorated clusters can be further used as building blocks for hierarchical self-assembly of larger structures. We address several important aspects of possible experimental implementation of the proposed scheme: the competition between different types of clusters in a solution, possible jamming in an unwanted configuration, and the degeneracy due to symmetry with respect to particle permutations.

cond-mat.soft

Error-proof programmable self-assembly of DNA-nanoparticle clusters

We study theoretically a new generic scheme of programmable self-assembly of nanoparticles into clusters of desired geometry. The problem is motivated by the feasibility of highly selective DNA-mediated interactions between colloidal particles. By analyzing both a simple generic model and a more realistic description of a DNA-colloidal system, we demonstrate that it is possible to suppress the glassy behavior of the system, and to make the self-assembly nearly error-proof. This regime requires a combination of stretchable interparticle linkers (e.g. sufficiently long DNA), and a soft repulsive potential. The jamming phase diagram and the error probability are computed for several types of clusters. The prospects for the experimental implementation of our scheme are also discussed. PACS numbers: 81.16.Dn, 87.14.Gg, 36.40.Ei

cond-mat.soft

Statistical Mechanics of DNA-Mediated Colloidal Aggregation

We present a statistical mechanical model of aggregation in colloidal systems with DNA mediated interactions. We obtain a general result for the two-particle binding energy in terms of the hybridization free energy $ΔG$ of DNA and two model dependent properties: the average number of available DNA bridges $\left< N\right>$ and the effective DNA conccentration $c_{eff}$. We calculate these parameters for a particular DNA bridging scheme. The fraction of all the $n$-mers, including the infinite aggregate, are shown to be universal functions of a single parameter directly related to the two-particle binding energy. We explicitly take into account the partial ergodicity of the problem resulting from the slow DNA binding-unbinding dynamics, and introduce the concept of angular localization of DNA linkers. In this way, we obtain a direct link between DNA thermodynamics and the global aggregation and melting properties in DNA-colloidal systems. The results of the theory are shown to be in quantitative agreement with two recent experiments with particles of micron and nanometer size. PACS numbers: 81.16.Dn, 82.20.Db, 68.65.-k, 87.14.Gg

cond-mat.stat-mech

Dynamics of particles with "key-lock" interactions

The dynamics of particles interacting by key-lock binding of attached biomolecules are studied theoretically. Examples of such systems include DNA-functionalized colloids as well as nanoparticles grafted with antibodies to cell membrane proteins. Depending on the coverage of the functional groups, we predict two distinct regimes separated by a percolation transition. In the localized regime at low coverage, the system exhibits a broad, power law like distribution of particle departure times. At higher coverage, there is an interplay between departure dynamics and particle diffusion. This interplay leads to a sharp increase of the departure times, a phenomenon qualitatively similar to aging in glassy systems. This diffusive regime is analogous to dispersive transport in disordered semiconductors: depending on the interaction parameters, the diffusion behavior ranges from standard diffusion to anomalous, subdiffusive behavior. The connection to recent experiments and implications for future studies are discussed.

cond-mat.soft