Cell migration: regulation of force on extracellular-matrix-integrin complexes

Sheetz, Michael P.; Felsenfeld, Dan P.; Galbraith, Catherine G.

doi:10.1016/s0962-8924(98)80005-6

Cited by 404 publications

(312 citation statements)

References 44 publications

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“…Because of the direct apposition and binding of the ECM proteins and cell cytoskeleton through cell receptors, cells sense and respond to the physical properties of the matrix by converting mechanical cues into intracellular chemical signals which drive activities such as gene expression, protein production, and general phenotypic behavior. 73,[175][176][177][178] Therefore, a primary goal in bone scaffold design is to mimic the unique micro and nanoscale characteristics of bone. In recent years, it has been well established in the literature that bone cells are profoundly influenced by topography in vitro.…”

Section: Physical Effectors In Synthetic Bone Scaffoldsmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

674

499

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Critical‐sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue‐engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical‐sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF‐βs, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009

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Section: Physical Effectors In Synthetic Bone Scaffoldsmentioning

confidence: 99%

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Porter

Ruckh

Popat

2009

Biotechnology Progress

674

499

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“…[84] Here, we discuss some of the many examples in which the ability of multivalent ligands to promote clustering has been used to reveal aspects of receptor function. [183][184][185] Integrin function is important in multicellular organisms, and targeted deletion of integrin subunits can strongly impair tissue formation. [186] Given their fundamental physiological roles, it is not surpising integrin-mediated adhesion and signaling events are carefully regulated.…”

Section: Receptor Proximitymentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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Cell surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Evidence from biochemical and structural studies indicates that many receptors do not operate as individual entities, but rather as part of higher-order complexes (e.g. dimers and oligomers). Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Despite the proposed importance of receptor-receptor processes in cellular signaling, questions concerning the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication remain unanswered.Chemical synthesis can provide a variety of compounds with which to address the role of receptor assembly in signal transduction. The focus of this review is one such approach -the use of synthetic multivalent ligands to characterize receptor function. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. Their unique architectures imbue multivalent ligands with the ability to access binding modes not available to monovalent compounds. Multivalent ligands, therefore, are capable of illuminating aspects of inter-receptor processes that are not readily probed using conventional approaches. We suggest that, as focus shifts from investigations of the function of individual proteins and toward the analysis of multi-receptor signaling complexes, multivalent ligands will become even more valuable tools with which to ask sophisticated mechanistic questions. Further, multivalent ligands may provide new opportunities for manipulating receptor systems for the deconvolution of pathways, diagnosis, and, ultimately, the treatment of disease.

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“…27,28 In our model, all this complexity is cast into four continuous two-dimensional ‡ (2D) elds: the deformable and moving interface (the cell's membrane) is described by an auxiliary phase eld [29][30][31][32] r(x, y; t) governed by an overdamped diffusive motion, cf. eqn (A.1), in a double-well model free energy.…”

Section: Brief Description Of the Modelmentioning

confidence: 99%

Modeling crawling cell movement on soft engineered substrates

2014

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Self-propelled motion, emerging spontaneously or in response to external cues, is a hallmark of living organisms. Systems of self-propelled synthetic particles are also relevant for multiple applications, from targeted drug delivery to the design of self-healing materials. Self-propulsion relies on the force transfer to the surrounding. While self-propelled swimming in the bulk of liquids is fairly well characterized, many open questions remain in our understanding of self-propelled motion along substrates, such as in the case of crawling cells or related biomimetic objects. How is the force transfer organized and how does it interplay with the deformability of the moving object and the substrate? How do the spatially dependent traction distribution and adhesion dynamics give rise to complex cell behavior? How can we engineer a specific cell response on synthetic compliant substrates? Here we generalize our recently developed model for a crawling cell by incorporating locally resolved traction forces and substrate deformations.The model captures the generic structure of the traction force distribution and faithfully reproduces experimental observations, like the response of a cell on a gradient in substrate elasticity (durotaxis). It also exhibits complex modes of cell movement such as "bipedal" motion. Our work may guide experiments on cell traction force microscopy and substrate-based cell sorting and can be helpful for the design of biomimetic "crawlers" and active and reconfigurable self-healing materials.

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Cell migration: regulation of force on extracellular-matrix-integrin complexes

Cited by 404 publications

References 44 publications

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Bone tissue engineering: A review in bone biomimetics and drug delivery strategies

Synthetic Multivalent Ligands as Probes of Signal Transduction

Modeling crawling cell movement on soft engineered substrates

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