| 1. Domain | 1.1 Scope of the Domain | Boundaries | The range of phenomena the science includes and excludes. | Focuses on functional behavior of cells, tissues, and multicellular structures above the cellular scale. Includes membrane transport, epithelial and connective tissue functions, muscle contraction, signaling integration, and mechanical/biophysical tissue properties. Excludes organ-level physiology and whole-system regulation except where directly determined by cellular/tissue mechanisms. |
| | Scale | The spatial, temporal, or organizational level at which the science operates (e.g., quantum, cellular, social, cosmic). | Operates at cellular to supracellular scales: nanometer-scale molecular interactions, micrometer-scale cell function, and millimeter-scale tissue structure across time spans from milliseconds to hours. |
| 1.2 Ontological Commitments | Entities | The kinds of things assumed to exist within the domain (particles, organisms, agents, fields, etc.). | Cells, tissues, extracellular matrix, cell junctions, membranes, ion channels, receptors, cytoskeleton, interstitial fluid, signaling molecules, contractile proteins, and mechanical load-bearing structures. |
| | Properties | The fundamental attributes these entities possess (mass, charge, genotype, preference, etc.). | Membrane potential, permeability, stiffness, elasticity, contractility, ion gradients, receptor sensitivity, mechanical tension, transport capacity, and tissue compliance. |
| | Categories | The basic ontological types used to classify domain elements (substances, processes, relations, structures). | Cell types, tissue types (epithelial, connective, muscle, nervous), transport processes, mechanical behaviors, signaling modes, junction types, and extracellular structures. |
| 1.3 State-Variables | Variables | The measurable or definable properties that describe system conditions. | Membrane voltage, ion concentrations, osmotic gradients, tension/pressure, intracellular Ca²⁺ levels, transport rates, mechanical strain, signaling activity, and tissue hydration. |
| | Parameterization | How variables encode and represent the system’s state. | State encoded via electrophysiological measurements, transport kinetics, mechanical-force curves, biochemical signaling profiles, fluid-pressure metrics, and tissue-structure indices. |
| 1.4 Admissible Idealizations | Simplifications | Conceptual reductions used to make the domain tractable (point masses, rational agents, perfect gases). | Treating tissues as homogeneous, modeling membranes as simple resistors/capacitors, assuming linear mechanical responses, collapsing complex signaling networks into single pathways, or ignoring heterogeneous microenvironments. |
| | Validity Conditions | The limits and contexts in which idealizations hold or break down. | Simplifications fail during nonlinear mechanical deformation, complex multi-ion coupling, heterogeneous tissue architecture, rapid dynamic signaling, or pathological structural changes. |
| 1.5 Domain Assumptions | Structural Assumptions | Background ontological stances such as determinism, continuity, randomness, discreteness. | Assumes deterministic ion transport, continuous electrophysiological behavior, stable biophysical laws governing tension/pressure, consistent membrane-channel function, and interpretable signaling cascades. |
| | Implicit Commitments | Unstated but necessary assumptions that shape the field’s conceptual structure. | Assumes cells behave consistently under similar conditions, tissues maintain characteristic mechanical/transport properties, and microenvironmental conditions meaningfully shape physiological behavior. |
| 1.6 Internal Coherence Requirements | Consistency | The demand that domain concepts do not contradict one another. | Electrical, mechanical, transport, and signaling descriptions must align without contradictions across cellular and tissue scales. |
| | Compatibility | The requirement that entities, variables, and assumptions fit together into a unified descriptive framework. | Entities (cells, ECM, channels), variables (voltage, tension, transport), and assumptions (continuity, determinism) must integrate into a unified framework of cellular and tissue function. |
| 2. Evidence Layer | 2.1 Observable Phenomena | Observables | The aspects of the domain that can produce detectable signals accessible to measurement. | Membrane potentials, ion fluxes, intracellular Ca²⁺ signals, mechanical deformation, contraction events, epithelial transport rates, tissue stiffness, and changes in cell morphology. |
| | Detection Limits | The boundaries of what can be resolved or sensed by current instruments or methods. | Minimum detectable ion concentration change, smallest measurable voltage fluctuation, lower limit of force or displacement detection, optical resolution boundaries for cell/tissue imaging, and sensitivity thresholds of biochemical reporters. |
| 2.2 Measurement Systems | Units | Standardized quantifications (meters, seconds, volts, decibels, dollars, etc.) necessary for consistent comparison. | mV (membrane potential), pA/pF (ionic current densities), µm (cell/tissue dimensions), Pa (pressure), nN–µN (force), molarity, fluorescence intensity, and time units from ms to hours. |
| | Instruments | Devices and tools (microscopes, spectrometers, sensors, surveys, detectors) used to produce measurements. | Patch-clamp amplifiers, calcium imaging systems, confocal/fluorescence microscopes, AFM for mechanics, microfluidic chambers, tension transducers, impedance analyzers, and biosensors. |
| 2.3 Operational Definitions | Definitions | Terms defined by specific measurement procedures, ensuring empirical clarity. | Operational definitions for “action potential,” “transport rate,” “tissue stiffness,” “permeability,” “contractile force,” and “epithelial barrier integrity,” tied to specific instrumentation and thresholds. |
| | Procedures | The explicit steps required to perform a measurement in a reproducible way. | Standard procedures such as patch-clamp recordings, immunostaining, permeability assays, microindentation for stiffness, Ca²⁺-indicator loading, and controlled mechanical/chemical stimulation protocols. |
| 2.4 Data Acquisition | Protocols | Formal processes for gathering data under controlled or standardized conditions. | Controlled recording sessions, time-lapse imaging sequences, force-measurement cycles, transport-rate assays, multi-condition stimulation tests, and repeated physiological trials. |
| | Sampling | Rules determining which subset of the domain is measured and how representative it is. | Rules for selecting cell types, tissue regions, time intervals, mechanical loads, chemical stimuli, and replicate numbers ensuring representative physiological measurements. |
| 2.5 Data Character & Format | Data Types | The form raw evidence takes (time series, spectra, images, counts, qualitative records). | Electrophysiological traces, fluorescence time series, force–displacement curves, transport-rate tables, confocal image stacks, tissue-mechanics datasets, and biochemical readouts. |
| | Resolution | The granularity or precision with which data is captured. | Temporal resolution (µs–ms for electrophysiology; seconds–minutes for signaling), spatial resolution (nm–µm microscopy), and mechanical resolution (nN–µN force sensitivity). |
| 2.6 Reliability & Calibration | Calibration | Adjustment procedures ensuring instruments produce accurate results. | Calibration of amplifiers, fluorescence baselines, force sensors, mechanical indenters, flow rates in microfluidics, and reference-standard solutions for transport and ion-measurement assays. |
| | Error Characterization | Identification and quantification of noise, uncertainty, bias, and measurement error. | Sources of noise including electrical drift, bleaching in fluorescence imaging, tissue heterogeneity, probe-loading variability, mechanical-slip error, and variance in biological replicates. |
| 3. Structural Layer | 3.1 Patterns & Regularities | Laws / Relations | Stable, repeatable patterns governing how observables behave across conditions. | Consistent physiological principles such as membrane voltage–current relationships, length–tension curves in muscle, stress–strain relationships in tissues, osmotic and electrochemical gradients, and rate–force coupling. |
| | Invariants | Quantities or properties that remain constant under transformations (symmetries, conservation laws). | Conserved biophysical quantities including resting membrane potential ranges, constant ion-equilibrium potentials (given ion ratios), characteristic elastic moduli of tissues, and reproducible Ca²⁺ signaling motifs. |
| 3.2 Causal Architecture | Mechanisms | Underlying processes or structures that produce the observed regularities. | Ion-channel gating, active transport cycles, mechanotransduction, excitation–contraction coupling, epithelial transport mechanisms, cytoskeletal force generation, and mechanical load distribution in tissues. |
| | Pathways | Organized sequences of interactions forming a causal chain or network. | Ordered processes such as depolarization → Ca²⁺ influx → contraction; ligand binding → signaling cascade → transport regulation; or mechanical load → cytoskeletal reorganization → altered tissue stiffness. |
| 3.3 Theoretical Vocabulary | Concepts | Core terms that encode the domain’s structure (force, gene, equilibrium, field). | Key terms include membrane potential, permeability, conductance, tension, compliance, mechanosensitivity, transport kinetics, junctional integrity, homeostasis, and biophysical coupling. |
| | Classifications | Taxonomies, categories, or typologies that organize entities and relations. | Categories such as epithelial vs connective vs muscle vs nervous tissue, passive vs active transport, mechanical vs biochemical signaling, ion-channel types, and cytoskeletal filament systems. |
| 3.4 Formal Representations | Equations | Mathematical constructs expressing laws, relations, or mechanisms. | Nernst equation, Goldman–Hodgkin–Katz equation, Ohm’s law analogs for membranes, Hill equation for muscle force, stress–strain curves, and Michaelis–Menten approximations for transport. |
| | Models | Structured representations—mathematical, computational, or conceptual—used to predict and explain phenomena. | Hodgkin–Huxley models, cross-bridge muscle models, epithelial transport models, cell-mechanics models, tissue-elasticity models, and biomechanical finite-element simulations. |
| 3.5 Idealized Structures | Simplified Models | Purposeful abstractions that capture essential dynamics while omitting irrelevant detail. | Linear membrane models, two-state channel models, homogeneous-tissue approximations, simplified viscoelastic models, reduced cytoskeletal network models, or single-pathway signaling abstractions. |
| | Limit Conditions | Regimes where specific models or approximations hold (classical vs. quantum, linear vs. nonlinear). | Valid under small deformations, moderate ion gradients, steady-state signaling, low-frequency mechanical loading, and healthy tissue structure; fail under nonlinear strain, rapid dynamics, pathological remodeling, or mixed ion-coupling regimes. |
| 3.6 Integrative Frameworks | Unifying Theories | Higher-order structures that connect disparate laws or mechanisms under a coherent whole. | Frameworks linking electrical, chemical, and mechanical processes—such as excitation–contraction coupling, mechano-electrochemical integration, tissue homeostasis theory, and multi-scale coupling models. |
| | Interdisciplinary Links | Points where the theory connects to adjacent sciences or larger explanatory systems. | Strong ties to biophysics, biomechanics, molecular biology, biomedical engineering, electrophysiology, and materials science through shared principles of force, transport, and structure. |
| 4. Method Layer | 4.1 Inquiry Design | Experimental Design | Structured plans for manipulating variables to test causal claims. | Manipulating ion concentrations, membrane potentials, mechanical loads, chemical stimuli, fluid flow, or substrate stiffness to test causal effects on cellular and tissue functional behavior. |
| | Observational Design | Systematic approaches for gathering non-manipulated data (surveys, field studies, natural experiments). | Recording natural cellular activity, spontaneous electrical behavior, mechanical responses, tissue deformation, transport activity, and unstimulated signaling without direct manipulation. |
| 4.2 Testing & Validation | Hypothesis Testing | Procedures for evaluating whether evidence supports or contradicts specific claims. | Evaluating predictions about ion-channel function, transport regulation, mechanical coupling, tissue stiffness changes, or signal–response relationships using targeted stimuli or perturbations. |
| | Replication | The requirement that results be independently reproducible under similar conditions. | Repeating electrophysiological recordings, imaging trials, mechanical tests, transport assays, and biochemical activation measurements across multiple cells, tissues, and experimental sessions. |
| 4.3 Inference & Evaluation | Statistical Inference | Rules for drawing conclusions from noisy or incomplete data. | Using regression, nonlinear curve fitting (e.g., I–V curves), ANOVA, mixed models, time-series analysis, dose–response statistics, and Bayesian inference to interpret physiological datasets. |
| | Model Comparison | Criteria (fit, simplicity, predictive accuracy, robustness) used to evaluate competing models. | Comparing alternative transport models, electrical models, mechanical models, or combined electro–mechanical frameworks based on fit, explanatory power, and predictive accuracy. |
| 4.4 Error Management | Error Analysis | Identification and quantification of random and systematic errors. | Identifying noise from electrical drift, optical photobleaching, mechanical sensor variance, probe-loading inconsistencies, tissue heterogeneity, and temporal instability in cell responses. |
| | Bias Control | Methods for minimizing subjective, instrumental, or procedural biases. | Standardizing stimulus intensity, calibration of sensors, blinded analysis of imaging/mechanical data, consistent patch-clamp criteria, replicates across tissue regions, and controlled environmental conditions. |
| 4.5 Adjudication & Revision | Peer Scrutiny | Collective evaluation of claims through critique, review, and debate. | Independent evaluation of physiological recordings, mechanical models, transport frameworks, and imaging analyses through peer review, replication attempts, and comparative multi-lab assessment. |
| | Theory Revision | Procedures for modifying, replacing, or discarding models based on new evidence. | Updating models of ion transport, contractile mechanics, epithelial barrier function, or cytoskeletal integration when new physiological evidence contradicts existing assumptions. |
| 4.6 Integrity Conditions | Transparency | Requirements to disclose methods, data, assumptions, and limitations. | Full reporting of stimulus protocols, recording settings, imaging parameters, mechanical calibration curves, solution compositions, analysis pipelines, and model assumptions. |
| | Ethical Standards | Norms ensuring responsible conduct in experimentation, data handling, and publication. | Ensuring cellular/tissue integrity, minimizing experimental damage, following ethical sourcing of tissues, honest reporting of data, and proper handling of experimental artifacts. |