Regenerative Adaptation to Electrochemical Perturbation in Planaria: A Molecular Analysis of Physiological Plasticity.

Anatomical homeostasis results from dynamic interactions between gene expression, physiology, and the external environment. Owing to its complexity, this cellular and organism-level phenotypic plasticity is still poorly understood. We establish planarian regeneration as a model for acquired tolerance to environments that alter endogenous physiology.

Neural control of body-plan axis in regenerating planaria.

Control of axial polarity during regeneration is a crucial open question. We developed a quantitative model of regenerating planaria, which elucidates self-assembly mechanisms of morphogen gradients required for robust body-plan control. The computational model has been developed to predict the fraction of heteromorphoses expected in a population of regenerating planaria fragments subjected to different treatments, and for fragments originating from different regions along the anterior-posterior and medio-lateral axis.

Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach.

We review the basic concepts involved in bioelectrically-coupled multicellular domains, focusing on the role of membrane potentials (V). In the first model, single-cell V is modulated by two generic polarizing and depolarizing ion channels, while intercellular coupling is implemented via voltage-gated gap junctions. Biochemical and bioelectrical signals are integrated via a feedback loop between V and the transcription and translation of a protein forming an ion channel.

Planarian regeneration as a model of anatomical homeostasis: Recent progress in biophysical and computational approaches.

Planarian behavior, physiology, and pattern control offer profound lessons for regenerative medicine, evolutionary biology, morphogenetic engineering, robotics, and unconventional computation. Despite recent advances in the molecular genetics of stem cell differentiation, this model organism's remarkable anatomical homeostasis provokes us with truly fundamental puzzles about the origin of large-scale shape and its relationship to the genome. In this review article, we first highlight several deep mysteries about planarian regeneration in the context of the current paradigm in this field.

Bioelectrical control of positional information in development and regeneration: A review of conceptual and computational advances.

Positional information describes pre-patterns of morphogenetic substances that alter spatio-temporal gene expression to instruct development of growth and form. A wealth of recent data indicate bioelectrical properties, such as the transmembrane potential (V), are involved as instructive signals in the spatiotemporal regulation of morphogenesis. However, the mechanistic relationships between V and molecular positional information are only beginning to be understood.

HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns.

Endogenous bioelectrical signaling coordinates cell behaviors toward correct anatomical outcomes. Lack of a model explaining spatialized dynamics of bioelectric states has hindered the understanding of the etiology of some birth defects and the development of predictive interventions. Nicotine, a known neuroteratogen, induces serious defects in brain patterning and learning.

Clinical Application of Mathematical Long Bone Ratios to Calculate Appropriate Donor Limb Lengths in Bilateral Upper Limb Transplantation.

Limited methods exist to aid in deciding the appropriate donor limb lengths in bilateral upper limb amputees qualifying for vascularized composite allotransplantation. We hypothesized mathematical equations could be created using long bone length ratios, and applied to radiographs, to approximate the patient's limb length prior to amputation. A data set of 30 skeletons' unilateral upper limb long bones measured using osteometric board and calipers was used.

Bioelectric gene and reaction networks: computational modelling of genetic, biochemical and bioelectrical dynamics in pattern regulation.

Gene regulatory networks (GRNs) describe interactions between gene products and transcription factors that control gene expression. In combination with reaction-diffusion models, GRNs have enhanced comprehension of biological pattern formation. However, although it is well known that biological systems exploit an interplay of genetic and physical mechanisms, instructive factors such as transmembrane potential () have not been integrated into full GRN models.

Exploring Instructive Physiological Signaling with the Bioelectric Tissue Simulation Engine.

Bioelectric cell properties have been revealed as powerful targets for modulating stem cell function, regenerative response, developmental patterning, and tumor reprograming. Spatio-temporal distributions of endogenous resting potential, ion flows, and electric fields are influenced not only by the genome and external signals but also by their own intrinsic dynamics. Ion channels and electrical synapses (gap junctions) both determine, and are themselves gated by, cellular resting potential.

Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms.

The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed of many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis and regeneration. Planarian flatworms are a popular system for exploring body plan patterning due to their regenerative capacity, but despite considerable molecular information regarding stem cell differentiation and basic axial patterning, very little is known about how distinct head shapes are produced.

Fundamental ratios and logarithmic periodicity in human limb bones.

Fundamental mathematical relationships are widespread in biology yet there is little information on this topic with regard to human limb bone lengths and none related to human limb bone volumes. Forty-six sets of ipsilateral upper and lower limb long bones and third digit short bones were imaged by computed tomography. Maximum bone lengths were measured manually and individual bone volumes calculated from computed tomography images using a stereologic method.

Growth of calcium phosphates on magnesium substrates for corrosion control in biomedical applications via immersion techniques.

Magnesium (Mg) has been suggested as a revolutionary biodegradable replacement for current permanent metals used in orthopedic applications. Current investigations concentrate on the control of the corrosion rate to match bone healing. Calcium phosphate coatings have been a recent focus of these investigations through various coating protocols.

Structural evidence for electromagnetic resonance in plant morphogenesis.

How a homogeneous collective of cells consistently and precisely establishes long-range tissue patterns remains a question of active research. This work explores the hypothesis of plant organs as resonators for electromagnetic radiation. Long-range structural patterns in the developing ovaries and male flower buds of cucurbit plants (zucchini, acorn, and butternut squash), in addition to mature cucurbit fruits (acorn, butternut, and zucchini squash; watermelon, and cucumber), were investigated.

Endogenous electromagnetic fields in plant leaves: a new hypothesis for vascular pattern formation.

Electromagnetic (EM) phenomena have long been implicated in biological development, but few detailed, practical mechanisms have been put forth to connect electromagnetism with morphogenetic processes. This work describes a new hypothesis for plant leaf veination, whereby an endogenous electric field forming as a result of a coherent Frohlich process, and corresponding to an EM resonant mode of the developing leaf structure, is capable of instigating leaf vascularisation. In order to test the feasibility of this hypothesis, a three-dimensional, EM finite-element model (FEM) of a leaf primordium was constructed to determine if suitable resonant modes were physically possible for geometric and physical parameters similar to those of developing leaf tissue.

Describing long-range patterns in leaf vasculature by metaphoric fields.

Some patterns in dicotyledonous leaf vasculature depict rather precise, long-range structural features. This work identifies and quantifies these previously unrecognized features in terms of an empirically derived mathematical formalism that generates wave-like spatial patterns referred to as metaphoric fields. These patterns were used to specify regularities in the long-range structure of dicot leaf vasculature, and were found to account significantly for the predominant features of all 27 dicot species studied.

Seeing tissue as a 'phase of matter': exploring statistical mechanics for the cell.

The field of tissue engineering aims to produce living, biological constructs which possess the appropriate spatial ordering of cells and their extra cellular matrix products. The complexity of a single cell and its interactions in a large collective have made development of useful models to assist in tissue culture difficult, and consequentially most tissue culture endeavors are limited to trial and error approaches. Some cell types display a natural tendency to spontaneously self-assemble into large domains of parallel-oriented cells.

Bone-like matrix formation on magnesium and magnesium alloys.

Mg metal and its alloys have promise as a biocompatible, degradable biomaterials. This work evaluates the potential of in vitro cell culture work with osteoblast-like cells on Mg based materials, and investigates cell differentiation and growth on Mg alloyed with various non-toxic or low-toxicity elements. Mg based substrates support the adhesion, differentiation and growth of stromal cells towards an osteoblast-like phenotype with the subsequent production of a bone like matrix under in vitro conditions.

Silicon substitution in the calcium phosphate bioceramics.

Silicon (Si) substitution in the crystal structures of calcium phosphate (CaP) ceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP) generates materials with superior biological performance to stoichiometric counterparts. Si, an essential trace element required for healthy bone and connective tissues, influences the biological activity of CaP materials by modifying material properties and by direct effects on the physiological processes in skeletal tissue. The synthesis of Si substituted HA (Si-HA), Si substituted alpha-TCP (Si-alpha-TCP), and multiphase systems are reviewed.

Magnesium and its alloys as orthopedic biomaterials: a review.

As a lightweight metal with mechanical properties similar to natural bone, a natural ionic presence with significant functional roles in biological systems, and in vivo degradation via corrosion in the electrolytic environment of the body, magnesium-based implants have the potential to serve as biocompatible, osteoconductive, degradable implants for load-bearing applications. This review explores the properties, biological performance, challenges and future directions of magnesium-based biomaterials.

Functional atomic force microscopy investigation of osteopontin affinity for silicon stabilized tricalcium phosphate bioceramic surfaces.

Resorbable silicon stabilized tricalcium phosphate (Si-TCP)-based bioceramics are characterized from a biological perspective by measuring the intermolecular interaction force between osteopontin (OPN) protein and the material surface using atomic force microscopy (AFM). OPN protein was covalently bound to silicon nitride AFM tips and adsorption and adhesion forces were measured in an electrolyte with a composition similar to that of physiological fluids. A strong relationship exists between the adhesion force of OPN on the material surface, the number of adherent osteoclasts (OC) and the resorption of the material.

Electron spin resonance in silicon substituted apatite and tricalcium phosphate.

Impurity centers associated with silicon have been observed in the phase mixture of silicon substituted apatite (Si-Ap) and silicon stabilized tricalcium phosphate (Si-TCP) using electron spin resonance (ESR). Two unique centers occur upon addition of SiO2 to the calcium phosphate system: an orthorhombic center with g-values 2.0072+/-0.