English

• Biological cells depend on the proper functioning of sophisticated molecular machinery [1]. This is accomplished through constant sensing of changes in the extracellular environment and responding accordingly [2]. Such adaptive responses favor homeostatic physiology [3]. Inspired by the powerful signal transduction capabilities of biological cells, scientists are developing sensors [4], nanorobots [5], drug delivery systems [6], and other technologies based on these capabilities to meet challenges in the biosciences and medicine [7,8]. These bioinspired engineering technologies have potential for a wide range of applications in the future [1,9]. Although some progress has been made in these attempts, these bioinspired systems require more sophisticated design and construction.

  DNA is an important material for storing and encoding genetic information [10], but it has many research and application prospects in the fields of biosensing design [11–13], nanorobot construction [14,15], DNA computing and storage [16,17], DNA circuit development [18,19], and drug delivery owing to its unique programmability and designability [20–22]. In particular, researchers have, for example, designed specific signal transduction and feedback networks based on DNA strand displacement (DSD) [14,23,24]. DSD involve the displacement of an “placeholder” strand by a “overriding” strand by binding to a complementary region on the placeholder strand, often aided by a “toehold” that controls replacement. These DNA strand reactions have sparked a surge of interest in mimicking natural networks [25] with the goal of developing synthetic biomimetic systems that mimic natural processes [26,27]. Moreover, some studies are trying to combine DNA strand reactions with real biosystems to achieve signal transduction with the aim of controlling the transduction and feedback of cellular signals [28–30]. Consequently, DNA molecules have come to play an important role in construction of biomimetic cell-inspired systems [31,32]. Notwithstanding advances in DNA mimicry, we have just begun to explore the design and engineering of artificial biosystems using DNA as a building block.

  Inspired by these advances, we herein the design of a liposome-based DNA network using DSD to mimic immune signal transduction. Immune signal transduction, as the most basic biological process in the immune system, is carried out through a network of complex biological signaling [33]. In one pivotal study, researchers used DSD to simulate the cellular machinery involved in cell-mediated immune response [23]. This pioneering work laid the groundwork for expanding the use of DSD to build artificial systems that mimic biological activities [34,35]. Inspired by this, we designed immune signal transduction system using DNA strands and liposomes to mimic the process of antigen capture, phagocytosis, presentation, and T cell activation in cell-mediated immune response, which however, encompasses physiological T cell recognition and response to antigen signal, a critical part of adaptive immune response. To accomplish this in a stepwise manner, we (1) simulated antigen-presenting cells (mAPCs) fused with mimicking pathogens (mPs) using DNA reactions, followed by (2) transmitting the molecular information of mPs to the surface of mAPCs to form activated mimicking antigen-presenting cells (A-mAPCs). Then, (3) DNA strands on A-mAPCs, mimicking the major histocompatibility complex (MHC), opened DNA ion channels embedded in the membrane of mimic naïve T cells (mTCs), which acted as T-cell receptors (TCRs), thereby (4) simulating antigen presentation by activated APCs to naïve T cells. These DNA channels, opened via DSD, as described above, enabled Ca²⁺ ions to enter mTCs along a concentration gradient, thereby intensifying calcein fluorescence as a reporter of mTCs response. In this process, the DNA strands on the surface of A-mAPCs and the Ca²⁺ ions in the solution together act like costimulatory molecules on APCs, prompting various types of T cell responses, including those of effector T cells, memory T cells, regulatory T cells. Based on our results, we found that mimicking immune signal transduction system can continuously transmit and regulate simulated immune signals through a pathway of DSD, representing a significant step forward in applying DNA molecules to model biological processes.

  To successfully construct this artificial immune signal transduction system, a detailed design of biomimetic system was first carried out. We used liposomes with different DNA strands to simulate pathogens, APCs, and naïve T cells. These liposomes were then employed to mimic the processing and presentation of antigens by T cells, thereby initiating an adaptive cellular immune signal transduction through DSD (Fig. 1). DNA strands modified with cholesterol were inserted into liposome surfaces via hydrophobic interactions with phospholipids, followed by DSD to enable signal transduction between liposomes. When mAPCs encountered mPs, a series of DSD occurred, leading to DNA-mediated fusion of mAPCs and mPs. The “pathogenic signature” on the surface of mPs (antigen) was then processed and transmitted to the “membrane surface” of mAPCs in the form of DNA strands, which resulted in activating the antigen-presenting capacity of mAPCs. Next, A-mAPCs interacted with the DNA structure of mTCs through their surface DNA strands by presenting mPs (antigens). This interaction simulated the response of naïve T cells induced by activated APCs, converting naïve T cells into various types of T cells, such as effector T cells, memory T cells, and regulatory T cells. More specifically, the DNA strands on A-mAPCs, mimicking the MHC of APCs, opened DNA ion channels embedded in the membrane of mTCs, which acted as TCRs, poised to receive the influx of Ca²⁺ ions, thereby simulating antigen presentation by activated APCs for recognition by naïve T cells. The DNA strands on A-mAPCs and the Ca²⁺ ions in the solution act like costimulatory molecules on APCs. Thus, with a DNA-coded handshake, the molecular signature of mPs (antigen) is relayed to mTCs, causing the DNA ion channel, acting as TCRs, across the membrane of mimic naïve T cells (mTCs to open, allowing Ca²⁺ to flow into mTCs from the extracellular membrane through the DNA ion channel. As the inner concentration of Ca²⁺ increased, calcein green fluorescence within mTCs, as a reporter for mTC response, intensified.

  Figure 1

  

  Figure 1.  Schematic representation of natural and mimicking immune signal transduction process for pathogens identification and response. APCs uptake Pathogens: Mimicking antigen-presenting cells “engulf” pathogen mimics and transferring “pathogenic signature” to form activated mimicking antigen-presenting cells through DNA reactions. APCs activate T cells: DNA strands on activated mimicking antigen-presenting cells, mimicking MHC, opened DNA ion channels embedded in the membranes of mimic naïve T cells, functioning as TCRs. T cells response: mimicking the response of naïve T cells.

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  APCs initiate immune signal transduction by phagocytizing pathogens and undergoing activation. In this process, APCs, phagocytes that detect and engulf pathogens [36], present parts of ingested peptide on their surface after phagocytosis [37], which activates them. Consequently, we tried to simulate this process through DNA strand displayment-mediated liposome fusion. The mAPCs interact with the DNA strands on the surface of mPs through their surface-modified DNA strands, which are pulled closer together by DNA “zipping” resulting from DNA base pairing, ultimately leading to fusion. This completes the phagocytosis of mPs by mAPCs, while the DNA strands on the surface of mPs remain on the surface of mAPCs as “antigen signals” under the action of DSD (Fig. 2A). In detail, to ensure successful phagocytosis of mPs by mAPCs, we verified the DSD of DNA strands modified on the surfaces of both by polyacrylamide gel electrophoresis (PAGE, Fig. S2 in Supporting information). Fig. 1 and Fig. S1A (Supporting information) illustrated the reaction process of DSD. As shown in Fig. S2, lane 6 represented DNA recognition molecules on the surface of mAPCs, and lane 8 represented DNA molecules on the surface of mPs. When the two DNA strands were mixed, DSD occurred, as shown in lane 10. Simultaneously, as shown in lanes 5 and 6 and lane 10 of Fig. S2, the DSD mediated a “zippering” reaction between two DNA double strands. This “zippering” reaction brought mAPCs and mPs into close proximity and facilitate their fusion (Fig. 2A).

  Figure 2

  

  Figure 2.  Simulation of phagocytosis and processing of pathogens by antigen-presenting cells. (A) The illustration depicted the phagocytosis of mPs by mAPCs through DSD. (B) Kinetics analysis of phagocytosed mPs by mAPCs with excitation (ex.) at 460 nm and emission (em.) at 583 nm. (C) Kinetics analysis of DSD during phagocytosis of mPs by mAPCs (ex. 550 nm, em. 570 nm). (D, G, J) Illustration of fluorescent labeled mPs, mAPCs, and A-mAPCs. (E, H, and K) and (F, I, L) LSCM images of nitrobenzoxadiazolyl (NBD) (ex. 460 nm, em. 525 nm) and Cy3 (ex. 550 nm, em. 570 nm) fluorescence channels, corresponding to (D, G, and J), respectively. Scale bar: 1 µm.

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  To verify the phagocytosis of mPs by mAPCs, DNA strands were modified on their surfaces via cholesterol-phospholipid interactions (Fig. 2A). The phagocytosis process occurred in two steps. First, DNA-mediated liposome fusion simulated mAPCs engulfing mPs [38]. Second, DSD on both liposomes exposed the “antigen site”. To confirm fusion, N-Rh-PE and N-NBD-PE fluorescent phospholipids were added to the membranes of mPs and mAPCs, respectively. When mPs and mAPCs are mixed, the DNA strands modified on their surfaces interact with each other, mediating their fusion. The fluorescent lipid molecules carried by each come into proximity during the fusion process, resulting in an increase in the fluorescence intensity of N-Rh-PE under the excitation of N-NBD-PE due to the fluorescence resonance energy transfer (FRET) effect (Fig. S3 in Supporting information and Fig. 2B, gray dots). However, no significant fluorescence change was observed in liposomes without DNA modification, indicating no fusion (Fig. 2B, blue dots). Even though this confirmed that DNA strands facilitated the fusion and phagocytosis of mPs by mAPCs, we employed another FRET assay (Fig. 2C) to confirm exposure of the “antigen site”. To accomplish this, DNA strands were modified with Cy3 and Cy5 fluorescent molecules as illustrated in Fig. 2A. Upon mixing mPs and mAPCs, the DNA strands on their surfaces undergo a DSD reaction based on complementary pairing principles. Under the FRET effect, upon excitation of Cy3, the fluorescence emitted by Cy3 gradually decreases as Cy3 and Cy5 move closer due to DNA strand migration (Fig. 2C, yellow dots), and the energy of Cy3 is transferred to Cy5 as the DSD reaction proceeds. This confirmed that DNA strands migrated and recombined, exposing the “antigen site”. The laser scanning confocal microscopy (LSCM) imaging also confirmed the fusion of mAPCs with mPs. Fig. 2D shows Cy3 molecules on mPs and Fig. 2G shows N-NBD-PE on mAPCs. Figs. 2E and F indicated that NBD fluorescence was absent on mPs, while Cy3 was present. Figs. 2H and I show the presence of NBD fluorescence on mAPCs but no Cy3 signals. After mixing, A-mAPCs showed both NBD and Cy3 fluorescence (Figs. 2K and L), confirming successful phagocytosis of mPs by mAPCs through strand replacement. Then, the fluorescence of Cy3 and N-NBD-PE simultaneously appeared on A-mAPCs (Fig. 2J). To summarize, mPs undergo DSD, leading to their phagocytosis by mAPCs. The DNA strands on mPs functioned as antigen and were transmitted to “MHC” DNA strands on mAPCs, similar to MHC molecules that bind peptide fragments from pathogens and display them on the cell surface for T cells to recognize.

  The activation of naïve T cells in response to specific antigens presented by activated APCs is a crucial step in the immune response and a key process that we aim to mimic using DSD and liposomes [36]. Here, we focused on constructing mTCs using DNA ion channels and liposomes to emulate the effector function elicited during antigen presentation by A-mAPCs. When mTCs respond to antigen signal presented by A-mAPCs, DNA ion channels across the mTCs membrane play a role in mimicking both signal transduction and TCR function. Under normal conditions, cap strands on the exterior of the DNA ion channels shut them down, hindering the unrestricted entry of Ca²⁺ ions into mTCs. However, following the interaction between the DNA “antigen” strands on the surface of A-mAPCs and cap strands, DNA strand reaction between A-mAPCs and mTCs opens the ion channels across the mTCs membrane, allowing ions outside the mTCs to freely enter and causing the Calcein inside mTCs to emit green fluorescence.

  To build mTCs capable of performing signal transduction, a series of experiments was carried out. In Fig. S5A (Supporting information), the PAGE image showed the step-by-step assembly of DNA ion channels, indicating successful assembly. Moreover, as shown in lane 1 and lane 2 of Fig. S4 (Supporting information), the cap strands with FAM fluorescent molecules blocked the DNA ion channels. In Figs. S5B–D (Supporting information), flow cytometry (FCM) results confirmed that DNA ion channels, capped with complementary strands, were embedded the mTCs membrane, mimicking the TCR on naïve T cells. As shown in Fig. S5B, FCM detected no obvious fluorescence signals of the DNA ion channels and cap strands within blank liposomes. When DNA ion channels embedded in the membrane of the mTCs were labeled with Cy5 fluorescent molecules, FCM was able to detect the Cy5 fluorescence signals on mTCs (Fig. S5C). Meanwhile, the FCM result, as shown in Fig. S5D, displayed FAM-labeled cap strands bound to Cy5-labeled DNA ion channels embedded across the membrane of the mTCs. LSCM imaging results in Fig. S5E (Supporting information) also revealed that DNA ion channels with the cap strands were embedded across the mTCs membrane. Both Cy3 fluorescence, which displayed DNA ion channels, and FAM fluorescence, which displayed cap strands, were simultaneously localized on the membrane of mTCs (Fig. S5E). In the process of constructing mTCs using DNA ion channels, the middle part of the DNA ion channels is modified with the hydrophobic phosphothioate group, allowing the DNA ion channels to stably embed and remain in the phospholipid bilayer of the mTCs [26].

  Following the construction of artificial naïve T cells, we sought to model the interaction between T cells and activated APCs. Natural naïve T cells recognize and interact with the MHC on the membrane of APCs via TCR [39]. In our artificial construct, A-mAPCs achieve recognition of mTCs through the identification and interaction of DNA strands between A-mAPCs and mTCs. The “MHC” DNA strands on A-mAPCs interacted with DNA ion channels mimicking TCRs on mTCs. Through DSD, we then presented “antigen” DNA strands to mTCs, thereby opening the DNA ion channels and simulating the reception of antigen signals by naïve T cells. The “antigen” signal transmitted from A-mAPCs to mTCs mimicked the transduction of antigen signal from activated APCs to naïve T cells (Figs. 3A and B), as validated by PAGE (Fig. S4, lane 3), showing that the DNA ion channels were opened through base pairing illustrated in Fig. S1B. To more clearly demonstrate these DSD processes, we simplified the DNA strands of mAPCs and A-mAPCs, retaining the core strands for participation in the strand reactions, and tested them via PAGE (Fig. S4). As shown in lane 2 and lane 3 of Fig. S4, after mixing DNA ion channels with cap strands labeled with FAM fluorescent molecules and DNA strands of A-mAPCs, we can see that the FAM-labeled cap strands from the DNA ion channels paired with the DNA strands of A-mAPCs, resulting in the opening of most DNA ion channels. However, when mAPCs were not “antigen”-activated, along with the blocking of DNA reaction site with Cy5-labeled strands, FAM-labeled cap strands could not pair with A-mAPCs DNA strands, keeping the DNA ion channels closed (Fig. S4, lane 4).

  Figure 3

  

  Figure 3.  “Antigen” signal transduction from A-mAPCs to mTCs. (A, B) Schematic images illustrated DNA cap strands transmitted from A-mAPCs to mTCs. (C, D) LSCM images revealed the presence of Alexa Fluor 405 labeled cap strands on A-mAPCs. (E, F) LSCM images revealed the departure of Alexa Fluor 405-labeled cap strands from mTCs. (G) Illustration depicted interaction between mPs and mTCs (upper), interaction between A-mAPCs and mTCs (middle), mTCs (lower). (H) The results shown by FCM correspond to the content in the upper, middle, and lower sections of the schematic diagram in (G). Scale bar: 1 µm.

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  After validating DNA strand reactions, we modified DNA ion channels and DNA strands on liposomes to confirm the transduction of “antigen” signals from A-mAPCs to mTCs, simulating the recognition of naïve T cells. Figs. 3C–F show that DNA ion channels on mTCs opened, mimicking T cell recognition of MHC on APCs. N-NBD-PE labeled A-mAPCs interacted with Cy3-labeled DNA ion channels on mTCs, leading to increased Alexa Fluor 405 fluorescence on A-mAPCs (Figs. 3C and D) and decreased fluorescence on mTCs (Figs. 3E and F). This indicates that the DNA ion channels opened and that mTCs were identified. In this process, the DNA strands of A-mAPCs mimicked MHC, and the DNA ion channels of mTCs mimicked TCR. The strand displacement between A-mAPCs and mTCs was similar to the cross-talk between activated APCs and naïve T cells.

  Under normal conditions, naïve T cells require a higher threshold of recognition signals, and the efficiency of direct recognition of naïve T cells by pathogenic antigens without processing by APCs is very low [39]. As illustrated in Fig. 3G (upper), in the absence of mAPCs processing, the “antigen” DNA strands on mPs fail to interact with the “TCR” of mTCs, consequently preventing the recognition of mTCs by opening DNA ion channels. Correspondingly, as illustrated in Fig. 3H (upper), whenever mPs encounter mTCs without mAPCs processing, the FAM-labeled cap strands on the DNA ion channels embedded across mTCs membrane do not pair with DNA strands on mPs, displaying an inactive state of mTCs, as shown in Fig. 3G (lower) and Fig. 3H (lower). On the other hand, as depicted in Fig. 3G (middle), after mPs were processed by mAPCs and “antigen” DNA strands transmitted to mAPCs, the A-mAPCs further present “antigen” DNA strands to mTCs, leading to the faring of FAM-labeled cap strands with DNA strands on A-mAPCs and BHQ1 fluorescence (Fig. 3H, middle). Compared with Fig. 3H (lower), the FCM result of Fig. 3H (middle) revealed that mTCs were recognition by a change in fluorescent signal. To further validate this result, we swapped the modification sites of fluorescent molecules and BHQ1 so that FAM was placed on the DNA strand of mPs, while BHQ1 was placed on the cap strands (Fig. S6A). In the absence of processing by mAPCs, mPs could not directly interact with the cap strands of mTCs, and mTCs could not receive the “antigen” DNA strands from mPs (Fig. S6B in Supporting information). However, after mPs were processed by mAPCs, the processed “antigen” DNA strands carried by A-mAPCs could pair with the cap strands of mTCs, allowing mTCs to interact with the “antigen” DNA strands of A-mAPCs and triggering their “cross-talk” (Fig. S6B). As shown in Fig. 3H and Fig. S6, our system revealed that “antigen” DNA strands first must be processed by mAPCs before recognition by mTCs, which is consistent with physiological conditions.

  In physiological processes, the interaction between the peptide-MHC complex on the surface of APCs and the TCR on the surface of naïve T cells is insufficient to activate and elicit a response from naïve T cells; the involvement of costimulatory molecules, such as CD80 or CD86, is also necessary for APCs to activate and elicit a response of naïve T cells [40]. In this study, the DNA strands on A-mAPCs and the Ca²⁺ ions in the solution act like costimulatory molecules of APCs to induce responses of mTCs. We designed a process to simulate the response of naïve T cells, as shown in Figs. 4A–C. After mTCs with Cy3-labeled DNA ion channels interacted with A-mAPCs, the “MHC” DNA strands on A-mAPCs were paired with the Alexa Fluor 405-labeled “TCR” cap strands on mTCs, opening the DNA ion channels, resulting in the “antigen” signals “cross-talk” between A-mAPCs and mTCs (Figs. 4A and B). When ion channels of mTCs were opened, Ca²⁺ ions in the solution flowed from outside (high concentration) to the inside (low concentration) of mTCs membrane owing the concentration gradient along the open ion channels. The Ca²⁺ ions that flow into the inside of mTCs would enhance the green fluorescence of calcein, and this enhanced green fluorescence is used as reporter for mTCs response after interacting with “antigen” DNA strands (Fig. 4C).

  Figure 4

  

  Figure 4.  mTCs responded to antigen presentation of mAPCs. (A–C) Schematic images illustrated the responses of mTCs to interaction with A-mAPCs. (D, E) FCM results displayed the flow of Ca²⁺ ions flowed into mTCs through DNA ion channels without cap strands, enhancing green fluorescence of Calcein. (F, G) LSCM images showed cap strands dissociated from the DNA ion channel embedded in mTCs, leading to an influx of Ca²⁺ ions and enhanced green fluorescence of calcein. Scale bar: 0.5 µm.

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  In the following experiment, FCM was used to verify the “antigen” signals “cross-talk” between A-mAPCs and mTCs, and the response of mTCs was successfully observed. When the “cross-talk” occurred, the fluorescence intensity in the sum of Q2 and Q3 in Fig. 4E was reduced compared to that in Fig. 4D, indicating a decrease in the Cy5 fluorescence carried by mTCs. This suggests that the Cy5-labeled cap strands detached from the mTCs and the ion channels of mTCs were opened. At this point, comparing Q1 in Figs. 4D and E, we observed that when the ion channels of mTCs were opened, Ca²⁺ ions flowed into the mTCs through the ion channels, enhancing the calcein green fluorescence inside the mTCs. This enhanced green fluorescence represents the response of mTCs to the “antigen presentation” of mAPCs (Figs. 4A–C). Meanwhile, following Alexa Fluor 405 labeled-cap strands from mTCs paired with “MHC” strands on A-mAPCs, LSCM images also confirmed that the opening of Cy5-labeled DNA ion channels embedded in mTCs led to enhanced green fluorescence of calcein from the influx of Ca²⁺ ions (Figs. 4F and G). The DNA strands on A-mAPCs and the Ca²⁺ ions in the solution serve as costimulatory signal that induced mTCs responses. According to these findings, mTCs exhibited green fluorescence enhancement in response to “antigen” DNA strands on A-mAPCs. This enhanced green fluorescence mimicked the response of naïve T cells to antigen presentation of APCs (Figs. 4A–C).

  Inspired by the powerful signal transduction network of immune response processes, including APCs and naïve T cells, as herein studied, researchers have sought to simulate the process in the hope of using resultant artificial systems as a reference point to solve heretofore intractable biomedical problems [41]. Owing to the characteristics of base pairing in DNA, as well as its designability and ease of synthesis, DNA is often used as a bioinspired material to construct simulated biological cell systems [42]. Accordingly, in the present study, we combined DNA strand reactions and liposomes to simulate antigen presentation by APCs, as well as T cell immune recognition and response to the presence of pathogens. We showed that the simulated mPs and mAPCs were separately constructed to simulate pathogens and APCs. After mixing mPs and mAPCs, DNA strands on the surface of mAPCs undergo DNA displacement that result in mediating the phagocytosis of mPs by mAPCs, forming activated mAPCs. When A-mAPCs encountered mTCs, DNA strand reactions occurred again to mediate recognition between them. The DNA strands on A-mAPCs, functioning similarly to MHC on APCs, interacted with DNA ion channels that mimicking TCR on naïve T cells. This interaction led to the observed processes of “cross-talk” between A-mAPCs and mTCs, causing mTCs to respond to the “antigen” by exhibiting fluorescence enhancement through the influx of Ca²⁺, which served as a reporter for mTCs’ response. In this process, the DNA strands on A-mAPCs and the Ca²⁺ ions in the solution act like costimulatory molecules of APCs (peptide-MHC complex, CD80, CD86, etc.). Although in the artificial system, mTCs rely on mAPCs to simulate antigen presentation through DSD, there are still differences compared to the antigen presentation process in the natural immune system. Nonetheless, this study provides significant reference value for the construction of bio-inspired signal transduction systems and the design of more realistic artificial biological systems. It is anticipated that this simulated event in cell-mediated immune recognition and response will provide an important reference point for the development of new materials, such as bioinspired biosensors, DNA circuits, nanorobots, and drug delivery carriers.

  Declaration of competing interest

  The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  CRediT authorship contribution statement

  Haozhi Lei: Writing – review & editing, Writing – original draft, Visualization, Data curation, Conceptualization. Qian Xia: Writing – review & editing, Funding acquisition. Xiqiu Wang: Visualization, Data curation. Yang Sun: Writing – review & editing, Methodology, Data curation. Weihong Tan: Writing – review & editing, Writing – original draft, Supervision, Funding acquisition.

  Acknowledgments

  This work was supported by the National Natural Science Foundation of China (No. 82002241), National Key Research and Development Program of China (No. 2020YFA0909000) and “Clinic Plus” Outstanding Project (No. 2024ZY012) from Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine.

  Supplementary materials

  Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2025.110941.

  
  
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  Figure 1  Schematic representation of natural and mimicking immune signal transduction process for pathogens identification and response. APCs uptake Pathogens: Mimicking antigen-presenting cells “engulf” pathogen mimics and transferring “pathogenic signature” to form activated mimicking antigen-presenting cells through DNA reactions. APCs activate T cells: DNA strands on activated mimicking antigen-presenting cells, mimicking MHC, opened DNA ion channels embedded in the membranes of mimic naïve T cells, functioning as TCRs. T cells response: mimicking the response of naïve T cells.

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  Figure 2  Simulation of phagocytosis and processing of pathogens by antigen-presenting cells. (A) The illustration depicted the phagocytosis of mPs by mAPCs through DSD. (B) Kinetics analysis of phagocytosed mPs by mAPCs with excitation (ex.) at 460 nm and emission (em.) at 583 nm. (C) Kinetics analysis of DSD during phagocytosis of mPs by mAPCs (ex. 550 nm, em. 570 nm). (D, G, J) Illustration of fluorescent labeled mPs, mAPCs, and A-mAPCs. (E, H, and K) and (F, I, L) LSCM images of nitrobenzoxadiazolyl (NBD) (ex. 460 nm, em. 525 nm) and Cy3 (ex. 550 nm, em. 570 nm) fluorescence channels, corresponding to (D, G, and J), respectively. Scale bar: 1 µm.

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  Figure 3  “Antigen” signal transduction from A-mAPCs to mTCs. (A, B) Schematic images illustrated DNA cap strands transmitted from A-mAPCs to mTCs. (C, D) LSCM images revealed the presence of Alexa Fluor 405 labeled cap strands on A-mAPCs. (E, F) LSCM images revealed the departure of Alexa Fluor 405-labeled cap strands from mTCs. (G) Illustration depicted interaction between mPs and mTCs (upper), interaction between A-mAPCs and mTCs (middle), mTCs (lower). (H) The results shown by FCM correspond to the content in the upper, middle, and lower sections of the schematic diagram in (G). Scale bar: 1 µm.

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  Figure 4  mTCs responded to antigen presentation of mAPCs. (A–C) Schematic images illustrated the responses of mTCs to interaction with A-mAPCs. (D, E) FCM results displayed the flow of Ca²⁺ ions flowed into mTCs through DNA ion channels without cap strands, enhancing green fluorescence of Calcein. (F, G) LSCM images showed cap strands dissociated from the DNA ion channel embedded in mTCs, leading to an influx of Ca²⁺ ions and enhanced green fluorescence of calcein. Scale bar: 0.5 µm.

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