Quantifying stiffness and forces of tumor colonies and embryos using a magnetic microrobot

Abstract

Stiffness and forces are two fundamental quantities essential to living cells and tissues. However, it has been a challenge to quantify both 3D traction forces and stiffness (or modulus) using the same probe in vivo. Here, we describe an approach that overcomes this challenge by creating a magnetic microrobot probe with controllable functionality. Biocompatible ferromagnetic cobalt-platinum microcrosses were fabricated, and each microcross (about 30 micrometers) was trapped inside an arginine–glycine–apartic acid–conjugated stiff poly(ethylene glycol) (PEG) round microgel (about 50 micrometers) using a microfluidic device. The stiff magnetic microrobot was seeded inside a cell colony and acted as a stiffness probe by rigidly rotating in response to an oscillatory magnetic field. Then, brief episodes of ultraviolet light exposure were applied to dynamically photodegrade and soften the fluorescent nanoparticle–embedded PEG microgel, whose deformation and 3D traction forces were quantified. Using the microrobot probe, we show that malignant tumor–repopulating cell colonies altered their modulus but not traction forces in response to different 3D substrate elasticities. Stiffness and 3D traction forces were measured, and both normal and shear traction force oscillations were observed in zebrafish embryos from blastula to gastrula. Mouse embryos generated larger tensile and compressive traction force oscillations than shear traction force oscillations during blastocyst. The microrobot probe with controllable functionality via magnetic fields could potentially be useful for studying the mechanoregulation of cells, tissues, and embryos.

Toward Single Cell Tattoos: Biotransfer Printing of Lithographic Gold Nanopatterns on Live Cells

“…Yet others have shown that living cells can internalize microstructures, such as radio frequency identification (RFID), 12 force and pressure sensors, 13,14 barcodes, 15 magnetic antennas, 16 and microrobots. 17 These studies demonstrate the possibility of interfacing various materials with live cells and tissues. However, a lithographybased technique for systematically integrating nanomaterials onto live cells with a high spatial resolution and yield has yet to be realized.…”

“…To address this challenge, researchers have explored alternative approaches to creating biological interfaces, such as depositing force-mediating nanoparticles on cells or 3D bioprinting composite formulations of nanomaterials and cells. − However, these biocompatible techniques often possess limited throughput and resolution, especially at submicrometer length scales. Yet others have shown that living cells can internalize microstructures, such as radio frequency identification (RFID), force and pressure sensors, , barcodes, magnetic antennas, and microrobots . These studies demonstrate the possibility of interfacing various materials with live cells and tissues.…”

Modulating tumor mechanics with nanomedicine for cancer therapy

“…[185][186][187][188] In one seminal study, a hydrogel microsphere-based magnetic microrobot was designed to quantify both forces and stiffness of tumor colonies. 189 Although these hydrogel-based microspheres are promising, they are difficult to use for characterizing aberrant mechanical properties in tumor tissues in vivo. Nanoparticles are well known for easy modification and versatile functionalities.…”

Tunable photoinitiated hydrogel microspheres for direct quantification of cell-generated forces in complex three-dimensional environments

“…Most recent techniques are based on the polymerization of acrylamide, but several studies have utilized other materials, such as alginate or gelatin 24,25 , whose stiffness is harder to control and/or varies within a relatively narrow range, limiting their usability. Polyethylene glycol (PEG) allows for varying stiffness over a wide range and has desirable biocompatibility 26 , although its hydrolytic degradability and autooxidation activity might affect cell function and make it less suitable for applications requiring long-term cell culture. Stable polyacrylamide (PAAm) microspheres with adjustable size and stiffness can be fabricated and made biocompatible by functionalization.…”