细胞内吞纳米颗粒药物的数值模拟研究

受体介导的内吞是细胞与外界物质交换的常见方式. 采用配体修饰表面的纳米脂质体颗粒,将药物有针对性地投放到肿瘤细胞 以提高药物传输的效率,是药物传 输系统设计中的核心问题之一. 本文假设内吞是准静态过程,采用三维数学模型来模拟球状纳米颗粒的内吞,建立了包含绑定键的系统变形能方程,通过求 解能量方程的最小值,得到药物在每个内吞包裹阶段的变形以及药物的被动内吞所需最小能量,分析不同药物半径对内吞所 需最小能量的影响. 研究表明,细胞膜变形能与绑定键变形能占总能量的绝大部分,各组分随着包裹区域增加均有变化;在给定细胞膜和药物颗 粒的硬度、绑定键强度等物理特性下存在最优药物尺寸,使得内吞过程中总能耗最小;在药物内吞进行的后期,包裹区域边 缘的绑定键因伸长过大发生断裂,影响内吞的顺利完成. 本研究为受体介导的高效药物设计提供了理论支撑.      

Molecular dynamics simulation of diffusion of nanoparticles in mucus

The rapid diffusion of nanoparticles(NPs) through mucus layer is critical for efficient transportation of NPs-loaded drug delivery system. To understand how the physical and surface properties of NPs affect their diffusion in mucus, we have developed a coarse-grained molecular dynamics model to study the diffusion of NPs in modeled mucus layer. Both steric obstruction and hydrodynamic interaction are included in the model capable of capturing the key characteristics of NPs' diffusion in mucus. The results show that both particle size and surface properties significantly affect the diffusivities of NPs in mucus. Furthermore, we find rodlike NPs can gain a higher diffusivity than spherical NPs with the same hydrodynamic diameter. In addition, the disturbed environment can enhance the diffusivity of NPs. Our findings can be utilized to design mucus penetrating NPs for targeted drug delivery system.     

Coarse grained molecular dynamics and theoretical studies of carbon nanotubes entering cell membrane

Motivated by recent experimental observations that carbon nanotubes （CNT） can enter animal cells, here we conduct coarse grained molecular dynamics and theoretical studies of the intrinsic interaction mechanisms between CNT＇s and lipid bilayer. The results indicate that CNT-cell interaction is dominated by van der Waals and hydrophobic forces, and that CNT＇s with sufficiently small radii can directly pierce through cell membrane while larger tubes tend to enter cell via a wrapping mechanism. Theoretical models are proposed to explain the observed size effect in transition of entry mechanisms.     

Effect of pore shape on effective porothermoelastic properties of isotropic rocks

The present work is devoted to the determination of the macroscopic poroelastic and porothermoelastic properties of geomaterials or rock-like composites constituted by an isotropic matrix with embedded ellipsoidal inhomogeneities and/or pores randomly oriented. By considering the solution of a single ellipsoidal inhomogeneity in the homogenization problem it is possible to observe the significant influence of the shape of inhomogeneities on the effective porothermoelastic properties. In the particular case of microscopic and macroscopic isotropic behaviors, a closed form solution based on analytical integrate of the Eshelby solution for the single ellipsoidal inhomogeneity can be obtained for the randomly oriented distribution. This result completes the well known solutions in the limiting cases of spherical and penny shape inhomogeneities. Based on recent works on porous rock-like composites such as shales or argillites, an application of the developed solution to a two-level microporomechanics model is presented. The microporosity in homogenized at the first level, and multiple solid mineral phase inclusions are added at the second level. The overall porothermoelastic coefficients are estimated in the particular context of heterogeneous solid matrix. Numerical results are presented for data representative of isotropic rock-like composites.     

Novel one-step synthesis of silica nanoparticles from sugarbeet bagasse by laser ablation and their effects on the growth of freshwater algae culture

Scientific research involving nanotechnology has grown exponentially and has led to the development of engineered nanoparticles（NPs）.Silica NPs have been used in numerous scientific and technological applications over the past decade,necessitating the development of efficient methods for their synthesis.Recent studies have explored the potential of laser ablation as a convenient way to prepare metal and oxide NPs.Due to its high silica content,low cost,and widespread availability,sugarbeet bagasse is highly suitable as a raw material for producing silica NPs via laser ablation.In this study,two different NP production methods were investigated：laser ablation and NaOH treatment.We developed a novel,one-step method to produce silica NPs from sugarbeet bagasse using laser ablation,and we characterized the silica NPs using environmental scanning electron microscopy（ESEM）,energy dispersive spectrometry（EDS）,dynamic light scattering（DLS）,transmission electron microscopy（TEM）,attenuated total reflectanceFourier transform infrared spectroscopy（ATR-FT1R）,X-ray photoelectron spectroscopy（XPS） and Raman spectroscopy.EDS analysis and XPS confirmed the presence of silica NPs.The NPs produced by laser ablation were smaller（38-190 nm） than those produced by NaOH treatment（531-825 nm）.Finally,we demonstrated positive effects of silica NPs produced from laser ablation on the growth of microalgae,and thus,our novel method may be beneficial as an environmentally friendly procedure to produce NPs.     

Assembly of charged aerosols on non-conducting substrates via ion-assisted aerosol lithography (IAAL)

The development of ion-assisted aerosol lithography (IAAL) has enabled fabrication of complex three-dimensional nanoparticle (NP) structures on conducting substrates. In this work, the applicability of the IAAL technique was investigated on non-conducting substrates. The NP structure growth process on a non-conducting substrate was found to self-terminate and the structures subsequently repel incoming charged NPs and scatter them away. Electric field calculations supported the experimental findings and confirmed that the electric field distortions owing to charge build-up within the structures prevented additional NP deposition thereon. To regulate the charge build-up without compromising the number of NPs available for assembly, a corona discharger and an ion trap were implemented. By varying the number of ions available in the assembly process, an optimum level of ion injection was found that allowed for a prolonged (>120 min) assembly of NP structures on non-conducting substrates without the unwanted scattering of NPs.     

Novel one-step synthesis of silica nanoparticles from sugarbeet bagasse by laser ablation and their effects on the growth of freshwater algae culture

Scientific research involving nanotechnology has grown exponentially and has led to the development of engineered nanoparticles (NPs). Silica NPs have been used in numerous scientific and technological applications over the past decade, necessitating the development of efficient methods for their synthesis. Recent studies have explored the potential of laser ablation as a convenient way to prepare metal and oxide NPs. Due to its high silica content, low cost, and widespread availability, sugarbeet bagasse is highly suitable as a raw material for producing silica NPs via laser ablation. In this study, two different NP production methods were investigated: laser ablation and NaOH treatment. We developed a novel, one-step method to produce silica NPs from sugarbeet bagasse using laser ablation, and we characterized the silica NPs using environmental scanning electron microscopy (ESEM), energy dispersive spectrometry (EDS), dynamic light scattering (DLS), transmission electron microscopy (TEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR–FTIR), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. EDS analysis and XPS confirmed the presence of silica NPs. The NPs produced by laser ablation were smaller (38–190 nm) than those produced by NaOH treatment (531–825 nm). Finally, we demonstrated positive effects of silica NPs produced from laser ablation on the growth of microalgae, and thus, our novel method may be beneficial as an environmentally friendly procedure to produce NPs.     

An upper bound to the free energy of n-variant polycrystalline shape memory alloys

In the last two decades, the problem of computing the elastic energy of phase transforming materials has been studied by a variety of research groups. Due to the non-quasiconvexity of the underlying multi-well landscape, different relaxation methods have been used in order to estimate the quasiconvex envelope of the energy density, for which no explicit expression is known at present.This paper combines a recently developed lamination bound for monocrystalline shape memory alloys which relies on martensitic twinned microstructures with the work of Smyshlyaev and Willis [1998a. A ‘non-local’ variational approach to the elastic energy minimization of martensitic polycrystals. Proc. R. Soc. London A 454, 1573–1613]. As a result, a lamination upper bound for n-variant polycrystalline martensitic materials is obtained.The lamination bound is then compared with Reuß- and Taylor-type estimates. While, for given volume fractions, good agreement of lamination upper and convexification lower bounds is obtained, a comparison using energy-minimizing volume fractions computed from the various bounds yields larger differences. Finally, we also investigate the influence of the polycrystal's texture. For a strong ellipsoidal texture, we observe even better agreement of upper and lower bounds than for the case of isotropic statistics.     

截锥体头型弹丸低速斜入水实验研究

为研究截锥体头型弹丸在低速斜入水条件下,头部直径大小对入水空泡及弹道特性的影响,基于高速摄像方法,开展不同截锥体头型弹丸低速倾斜入水对比实验,得到了截锥体头弹丸头部直径大小对入水空泡、运动速度、俯仰角的影响规律。实验结果表明:截锥体头弹丸头部直径越大,尾部越早与空泡下壁面发生碰撞;头部直径大小对空泡深闭合时间几乎没有影响;弹丸空泡随头部直径增大而增大;头部直径过大或者过小均不利于入水稳定性;弹丸速度低于临界值时呈上升趋势,高于临界值时将呈现下降趋势。     

A finite-strain constitutive theory for electro-active polymer composites via homogenization

This paper presents a homogenization framework for electro-elastic composite materials at finite strains. The framework is used to develop constitutive models for electro-active composites consisting of initially aligned, rigid dielectric particles distributed periodically in a dielectric elastomeric matrix. For this purpose, a novel strategy is proposed to partially decouple the mechanical and electrostatic effects in the composite. Thus, the effective electro-elastic energy of the composite is written in terms of a purely mechanical component together with a purely electrostatic component, this last one dependent on the macroscopic deformation via appropriate kinematic variables, such as the particle displacements and rotations, and the change in size and shape of the appropriate unit cell. The results show that the macroscopic stress includes contributions due to the changes in the effective dielectric permittivity of the composite with the deformation. For the special case of a periodic distribution of electrically isotropic, spherical particles, the extra stresses are due to changes with the deformation in the unit cell shape and size, and are of order volume fraction squared, while the corresponding extra stresses for the case of aligned, ellipsoidal particles can be of order volume fraction, when changes are induced by the deformation in the orientation of the particles.     

The averaged mechanical properties of prismatic lattice formed by ellipsoidal inclusions

Summary The objective of this paper is to evaluate the averaged elastic properties of 3-D grained composites in which identical inclusions form a prismatic network interacting with the matrix material. The inclusions are of ellipsoidal shape with transverse circular sections located at the nodes of a doubly-periodic lattice with an orthogonal elementary cell. When the arrays of inclusions are set at equal spacings in normal directions through the thickness of the matrix, the material formed is an anisotropic composite with tetragonal symmetry at planes transverse to the fiber axis. The longitudinal and transverse elastic and shear moduli as well as the longitudinal Poisson's ratios of such composites are evaluated in this paper. The averaged properties are studied in terms of the aspect ratio and volume fraction of the inclusions as well as the relative rigidity of the constituent phases. Employing the Eshelby's theory for the stress field around a single ellipsoidal inhomogeneity, which is surrounded by the effective anisotropic material, and considering the Mori-Tanaka's concept for the mutual interaction of the neighboring inclusions, we may evaluate the averaged elastic properties of grained composites with aligned ellipsoidal inclusions at finite concentrations. The results provided in a closed-form solution concern the stiffness of 3-D grained composites with parallely dispersed ellipsoidal inclusions forming a prismatic network inside the principal material. It is shown that the stiffness is affected by both the geometry of the inclusions and their concentration. The use of different composite models in the analysis shows that intense variations of stiffness occur mainly in hard composites weakened by soft ellipsoidal inclusions. These findings come in full verification with experimental or theoretical results from the literature. Received 10 February 1998; accepted for publication 27 November 1998     

Magnetic nanoparticles for environmental and biomedical applications: A review

Engineered magnetic nanoparticles (MNPs) hold great potential in environmental, biomedical, and clinical applications owing to their many unique properties. This contribution provides an overview of iron oxide MNPs used in environmental, biomedical, and clinical fields. The first part discusses the use of MNPs for environmental purposes, such as contaminant removal, remediation, and water treatment, with a focus on the use of zero-valent iron, magnetite (Fe₃O₄), and maghemite (γ-Fe₂O₃) nanoparticles, either alone or incorporated onto membrane materials. The second part of this review elaborates on the use of MNPs in the biomedical and clinical fields with particular attention to the application of superparamagnetic iron oxide nanoparticles (SPIONs), which have gained research focus recently owing to their many desirable features such as biocompatibility, biodegradability, ease of synthesis and absence of hysteresis. The properties of MNPs and their ability to work at both cellular and molecular levels have allowed their application in vitro and in vivo including drug delivery, hyperthermia treatment, radio-therapeutics, gene delivery, and biotherapeutics. Physiochemical properties such as size, shape, and surface and magnetic properties as well as agglomeration of MNPs and methods to enhance their stability are also discussed.     

Mechanopathology of red blood cell diseases — Why mechanics matters

During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular structures. These alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape, deformability and adhesion. As such, knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ones. Here, we will present biomechanistic insights into red blood cell related diseases that manifest mechanical property changes and how they directly contribute to the pathophysiology of diseases. By conducting cell and molecular mechanics studies, not only can we elucidate changes in the structure-property-function relationship of diseased cells, we can also exploit the new knowledge gained to develop biomechanics based devices that may better detect and diagnose these diseases as well as help identify important biomechanical targets for possible therapeutic interventions.     

Stress concentration of an ellipsoidal inclusion of revolution in a semi-infinite body under biaxial tension

Summary This paper deals with the stress concentration problem of an ellipsoidal inclusion of revolution in a semi-infinite body under biaxial tension. The problem is formulated as a system of singular integral equations with Cauchy-type or logarithmic-type singularities, where unknowns are densities of body forces distributed in the r- and z-directions in semi-infinite bodies having the same elastic constants as the ones of the matrix and inclusion. In order to satisfy the boundary conditions along the ellipsoidal boundary, four fundamental density functions proposed in [24, 25] are used. The body-force densities are approximated by a linear combination of fundamental density functions and polynomials. The present method is found to yield rapidly converging numerical results for stress distribution along the boundaries even when the inclusion is very close to the free boundary. The effect of the free surface on the stress concentration factor is discussed with varying the distance from the surface, the shape ratio and the elastic modulus ratio. The present results are compared with the ones of an ellipsoidal cavity in a semi-infinite body.accepted for publication 11 November 2003     

A 3-D ellipsoidal flaw model for brittle fracture in compression

Engineering materials are rarely free of flaws. Mode I cracking from pre-existing flaws is the major cause of the brittle fracture in compression of materials such as concrete and rock. A 3-D ellipsoidal flaw model is used to show the significant influence of flaw geometry on crack initiation in uniform uniaxial, biaxial and triaxial compression. The model shows that the governing criterion for crack initiation may change from energy to stress with increasing crack size, and that for voids of similar size a spherical void is the most critical shape for crack initiation. The model thus provides a basis for a better understanding of both the phenomenon and the mechanism of brittle fracture in compression.     

Numerical study of opposed zero-net-mass-flow jet-induced erythrocyte mechanoporation

With the advantages of biosafety and efficiency, increasing attention has been paid to the devices for gene and macromolecular drug delivery based on mechanoporation. The transient pore formation on the cell membrane allows cargo transportation when the membrane areal strain is beyond the critical pore value and below the lysis tension threshold. Based on this principle, we propose a method to apply the proper fluid stress on cells moving in a microchannel under the action of zero-net-mass-flux (ZNMF) jets. In this study, an immersed finite element method (IFEM) is adopted to simulate the interaction between the cells and the fluid fields so as to investigate the cell movement and deformation in this mechanoporation system. To evaluate the efficiency of the cargo delivery, a pore integral is defined as the mean pore rate when the cell passes through the jet region. By analyzing the effects of the parameters, including the pressure gradient along the microchannel, the jet amplitude, and the jet frequency, on the pore integrals, a group of optimized parameters for cargo delivery efficiency are obtained. Additionally, the stability and safety of this system are analyzed in detail. These results are helpful in designing the mechanoporation devices and improving their efficiency of drug delivery.     

A critical review of ferritin as a drug nanocarrier: Structure,properties, comparative advantages and challenges

Ferritin stores and releases iron ions in mammals. It is globally important as a drug nanocarrier. This is because of its unique hollow-spherical structure, desirable stability and biological properties. Novel drug-loading approaches plus various functionalization approaches have been developed to improve ferritin in response to differing demands in disease treatments. Here, we critically review ferritin drug delivery and evaluate its diverse drug-loading and functionalization approaches, we: (1) Introduce basic structural and property information related to ferritin as a drug nanocarrier; (2) Contrast in detail the different means to load drugs and the selection of drug loading means; (3) Discuss multiple ferritin functionalization approaches, together with related advantages and potential risks; and, (4) Compare ferritin with alternative, commonly-used drug nanocarriers. We conclude that despite that no drugs based on ferritin are commercially available, the market potential for it is significant, and evaluate future research directions. Findings from this work will be of immediate benefit and interest to a wide range of researchers and manufacturers for drug delivery using ferritin.     

Molecular-dynamics of a 2D Model of the Shape Memory Effect

This work investigates the thermodynamic properties of a qualitative atomistic model for austenite–martensite transitions. The model, still in 2D, employs Lennard-Jones potentials for the determination of the atomic interactions. By use of two atom species it is possible to identify three stable lattice structures in 2D, interpreted as austenite and two variants of martensite. The model is described in the first part of the work [6] in detail. The present work studies the thermodynamic properties of the model concerning a small, 2-dimensional test assembly consisting of 41 atoms. The phase stability is investigated by exploitation of the condition of minimal free energy. The free energy is calculated from the thermal equation of state, which is measured in numerical tensile tests. In the second part of this work a chain of eleven 41-atom assemblies is investigated. The chain is interpreted as an idealized larger body, where the individual crystallites represent crystallographic layers allowing for the creation of micro structure. By use of tensile tests at various temperature conditions we sketch how such chain may exhibit quasi-plasticity, pseudo-elasticity and the shape memory effect.     

A microscopic damage model considering the change of void shape and application in the void closing

A microscopic damage model of ellipsoidal body containing ellipsoidal void for nonlinear matrix materials is developed under a particular coordinate. The change of void shape is considered in this model. The viscous restrained equation obtained from the model is affected by stress ∑_(ij), void volume fraction f, material strain rate exponent m as well as the void shape. Gurson's equation is modified from the numerical solution. The modified equation is suitable for the case of nonlinear matrix materials and changeable voids. Lastly, the model is used to analyze the closing process of voids.     

Growing actin networks regulated by obstacle size and shape

Growing actin networks provide the driving force for the motility of cells and intracellular pathogens. Based on the molecular-level processes of actin polymerization, branching, capping, and depolymerization, we have devel-oped a modeling framework to simulate the stochastic and cooperative behaviors of growing actin networks in pro-pelling obstacles, with an emphasis on the size and shape effects on work capacity and filament orientation in the grow-ing process. Our results show that the characteristic size of obstacles changes the protrusion power per unit length, with-out influencing the orientation distribution of actin filaments in growing networks. In contrast, the geometry of obstacles has a profound effect on filament patterning, which influ-ences the orientation of filaments differently when the drag coefficient of environment is small, intermediate, or large. We also discuss the role of various parameters, such as the aspect ratio of obstacles, branching rate, and capping rate, in affecting the protrusion power of network growth.