Mapping Nanomechanical Properties of Basal Surfaces in Metastatic Intestinal 3D Living Organoids with High‐Speed Scanning Ion Conductance Microscopy

Abstract

Studying mechanobiology is increasing of scientific interests in life science and nanotechnology since its impact on cell activities (e.g., adhesion, migration), physiology, and pathology. The role of apical surface (AS) and basal surface (BS) of cells played in mechanobiology is significant. The mechanical mapping and analysis of cells mainly focus on AS while little is known about BS. Here, high‐speed scanning ion conductance microscope as a powerful tool is utilized to simultaneously reveal morphologies and local elastic modulus (E) of BS of genotype‐defined metastatic intestinal organoids. A simple method is developed to prepare organoid samples allowing for long‐term BS imaging. The multiple nano/microstructures, i.e., ridge‐like, stress‐fiber, and E distributions on BS are dynamically revealed. The statistic E analysis shows softness of BS derived from eight types of organoids following a ranking: malignant tumor cells > benign tumor cells > normal cells. Moreover, the correlation factor between morphology and E is demonstrated depending on cell types. This work as first example reveals the subcellular morphologies and E distributions of BS of cells. The results would provide a clue for correlating genotype of 3D cells to malignant phenotype reflected by E and offering a promising strategy for early‐stage diagnosis of cancer.

Organoid assessment technologies

“…It can dynamically reveal the morphological correlation factor depending on cell types between basal surface of cells and local elastic modulus (E). 80 Long-term time-lapse imaging enables monitoring the viability and homogeneity of multiple organoids in parallel. 81 Analyzing the structural development of organoids is challenging due to their heterogeneity and abstract morphology.…”

“…High‐speed scanning ion conductance microscope for long‐term imaging is utilized to simultaneously reveal morphologies of organoids. It can dynamically reveal the morphological correlation factor depending on cell types between basal surface of cells and local elastic modulus (E) 80 …”

“…It can dynamically reveal the morphological correlation factor depending on cell types between basal surface of cells and local elastic modulus (E). 80 …”

A Low‐Cost, User‐Friendly Rheo‐Optical Compression Assay to Measure Mechanical Properties of Cell Spheroids in Standard Cell Culture Plates

“…Additionally, it offers a straightforward and economical alternative for measuring spatio-temporal biophysical changes in biological samples, addressing a significant current demand. [38][39][40][41][42][43][44]…”

Characterizing Chemical, Environmental, and Stimulated Subcellular Physical Characteristics of Size-Fractionated PMs Down to PM0.1

“…Using an electrolyte-filled nanopipette as a nanoprobe, a high-speed scanning ion conductance microscopy (HS-SICM) technique as a powerful tool , has been widely used to visualize morphological and mechanical characteristics of living cells and dynamical nanoparticle–cell interactions. − The unique working principle of SICM utilized ion current changes as feedback signals through a nanoprobe between two electrodes to control the tip–sample distance. Thanks to the above robust feedback mechanism of SICM, it allows noncontact revealing nanoscale 3D profiles of samples with rich surface morphology and other physicochemical properties, , especially for cell-related surface imaging.…”