Abstract
Magnetospirillum magneticum (AMB-1) are a species of magnetotactic bacteria (MTB) that are capable of orienting along the earth’s magnetic field lines through their organelles called magnetosomes. Many studies have shown that certain engineered bacteria can infect the tumor cells, resulting in a controlled death of a tumor. This work deals with a technique utilizing AMB-1 along a predefined path through magnetotaxis, which can pave a way for selective doping as well as isolation of the tumor cells from a group of healthy cells through a magnetic invasive assay. For such a control, a tiny mesh of vertical electrical coils each having a diameter of ∼3 mm is fabricated, which establishes the path for the bacteria to move along the magnetic field lines. The molecular dynamics (MD) simulations at the interface of the bacterial cell surface proteins (MSP-1 and flagellin) and Chinese hamster ovary (CHO) cell surface containing cytoplasmic and extracellular proteins (BSG, B2M, SDC1, AIMP1, and FOS) are shown to establish an association between the AMB-1 and the host CHO cells. It is found that the CHO protein structure is compromised, which disables the activation of its defense function, allowing the bacteria to interact and survive. The experimental demonstration involves the CHO cells’ interaction with the AMB-1 and isolation of selected CHO cells. It is found that AMB-1-integrated CHO cells successfully moved along the magnetic field lines generated by the coils. Statistical analysis performed for the assay showed that AMB-1 cells were found to be viable after co-incubating with CHO cells, and the number of viable cells post co-incubation over a period of 24 h showed a slight decrease in both cell population. Overall, 51% of AMB-1 cells and 67% of CHO cells were found viable 24 h post co-incubation. Scanning electron microscopy (SEM) along with energy-dispersive X-ray spectroscopy (EDAX) analysis revealed AMB-1/CHO cell morphology, the potential interaction between them, and the presence of magnetosomes with trace amounts of iron in the AMB-1-interacted CHO cells, confirming the successful AMB-1 integration.
Highlights
Cancer is a result of uncontrolled cell division and proliferation of cells and is the second leading cause of death in the world (Hanahan and Weinberg, 2011; Siegel et al, 2020)
We show the directional control of magnetotactic bacteria (MTB) using ∼3-mm-sized solenoid coils forming a network of tracks and the ability of these MTB cells to interact with the mammalian cells using an in vitro monolayer of Chinese hamster ovary (CHO) cells
When we observed the hanging drop under the light microscope, we could see the erratic movement of AMB-1 cells confirming the motility of the bacteria (Supplementary Video 2)
Summary
Cancer is a result of uncontrolled cell division and proliferation of cells and is the second leading cause of death in the world (Hanahan and Weinberg, 2011; Siegel et al, 2020). Chemotherapy, a non-invasive therapy, utilizes various anti-cancerous drugs for the treatment of cancer throughout the body including the metastasized tumors. The drawbacks of this therapy are the side effects to the normal healthy cells, low efficacy due to small concentration of drugs reaching the core of tumor because of the disrupted vascular network, and the resistance developed by cancer cells against the drugs either intrinsically or owing to the frequent usage or due to hypoxic tumor microenvironment (TME) (Teicher et al, 1981; Wouters et al, 2007; Li et al, 2008; Lippert et al, 2008). TME contains certain immune cells that suppress the response from the immune system (Fridman et al, 2012; Gajewski et al, 2013)
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